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Stool transplants may boost immunotherapy success in melanoma
, defined as complete response, partial response, or stable disease that lasted 6 months or longer. The results come from a small, single arm phase 1 study whose primary endpoint was safety.
“We know that the gut microbiome has shown the ability to affect the systemic antitumor immunity by affecting the CD8+ T cells and CD4+ T cells, and these are the cells that are ultimately important for the function of checkpoint inhibitors. There is now clinical evidence that has shown that changing patient microbiota via fecal microbiota transplantation using stool from previous responder patients has the capacity to sensitize immunotherapy refractory melanomas to anti–PD-1 therapy, (with) about 30% response in this setting,” said Saman Maleki, PhD, during his presentation of the results at the Society for Immunotherapy of Cancer’s 37th Annual Meeting. He also noted that broad-spectrum antibiotics have been shown to negatively influence responses to immunotherapy.
Rather than using stool from donors who responded to immunotherapy, the researchers chose instead to use stool from healthy donors.
The study included 20 patients with advanced melanoma who had not been treated with anti–PD-1 therapy. The median age was 75.5 years, 40% were female, and 75% had wild type BRAF. All patients underwent bowel prep and then received fecal transplants from healthy donors, followed by a 7-day engraftment period before initiating anti–PD-1 therapy in the form of nivolumab or pembrolizumab.
The primary endpoint of the study was safety, and no grade 3 or 4 toxicities were observed during the FMT, and safety signals associated with anti–PD-1 therapies were in line with previous experience.
Fifteen percent of patients had a complete response, 50% had a partial response, 15% had stable disease, and 20% had progressive disease. Seventy-five percent of patients had a complete response, partial response, or stable disease that lasted at least 6 months.
Analysis of the microbiomes showed much higher diversity in the donor microbiomes than in patients. “What was really interesting was that the success of engraftment and retention of the donor microbiome was really key in determining between responders and nonresponders. Responders had successful engraftment that lasted over time, and in nonresponders we did not see that,” said Dr. Maleki, who is a cancer immunology researcher at the University of Western Ontario, London.
They also saw differences between responders and nonresponders in how their microbiome evolved over time. Responders had enrichment in Ruminococcus callidus and other bacteria, while nonresponders had enrichment in different bacteria, among them Catabacter hongkongensis, which has previously been implicated as negatively impacting anti–PD-1 responses, according to Dr. Maleki.
Microbiomes from healthy donors had greater diversity than the patients. Following FMT, patients’ microbiomes increased regardless of clinical response to immunotherapy. However, the tendency for patients to trend toward and retain greater diversity over time was associated with treatment success. “What we saw that was key in patients’ response to immunotherapy was the ability of the patients to retain the donor microbiome. All patients’ microbiomes changed and shifted toward the donors’ post FMT. However, only the responders were able to keep the donor microbiome over time, and the nonresponders’ microbiomes reverted to the previous microbiome,” Dr. Maleki said.
The researchers also conducted a mouse version of the clinical trial. They transplanted mice with the baseline fecal samples of a human responder and then exposed the animals to tumors. They then conducted a second FMT with stool from the human donor, and the animals then responded to anti–PD-1 therapy. The results further confirm “that the donor still has the capacity to drive response in this setting,” Dr. Maleki said.
Dr. Maleki is a board member of IMV Inc.
, defined as complete response, partial response, or stable disease that lasted 6 months or longer. The results come from a small, single arm phase 1 study whose primary endpoint was safety.
“We know that the gut microbiome has shown the ability to affect the systemic antitumor immunity by affecting the CD8+ T cells and CD4+ T cells, and these are the cells that are ultimately important for the function of checkpoint inhibitors. There is now clinical evidence that has shown that changing patient microbiota via fecal microbiota transplantation using stool from previous responder patients has the capacity to sensitize immunotherapy refractory melanomas to anti–PD-1 therapy, (with) about 30% response in this setting,” said Saman Maleki, PhD, during his presentation of the results at the Society for Immunotherapy of Cancer’s 37th Annual Meeting. He also noted that broad-spectrum antibiotics have been shown to negatively influence responses to immunotherapy.
Rather than using stool from donors who responded to immunotherapy, the researchers chose instead to use stool from healthy donors.
The study included 20 patients with advanced melanoma who had not been treated with anti–PD-1 therapy. The median age was 75.5 years, 40% were female, and 75% had wild type BRAF. All patients underwent bowel prep and then received fecal transplants from healthy donors, followed by a 7-day engraftment period before initiating anti–PD-1 therapy in the form of nivolumab or pembrolizumab.
The primary endpoint of the study was safety, and no grade 3 or 4 toxicities were observed during the FMT, and safety signals associated with anti–PD-1 therapies were in line with previous experience.
Fifteen percent of patients had a complete response, 50% had a partial response, 15% had stable disease, and 20% had progressive disease. Seventy-five percent of patients had a complete response, partial response, or stable disease that lasted at least 6 months.
Analysis of the microbiomes showed much higher diversity in the donor microbiomes than in patients. “What was really interesting was that the success of engraftment and retention of the donor microbiome was really key in determining between responders and nonresponders. Responders had successful engraftment that lasted over time, and in nonresponders we did not see that,” said Dr. Maleki, who is a cancer immunology researcher at the University of Western Ontario, London.
They also saw differences between responders and nonresponders in how their microbiome evolved over time. Responders had enrichment in Ruminococcus callidus and other bacteria, while nonresponders had enrichment in different bacteria, among them Catabacter hongkongensis, which has previously been implicated as negatively impacting anti–PD-1 responses, according to Dr. Maleki.
Microbiomes from healthy donors had greater diversity than the patients. Following FMT, patients’ microbiomes increased regardless of clinical response to immunotherapy. However, the tendency for patients to trend toward and retain greater diversity over time was associated with treatment success. “What we saw that was key in patients’ response to immunotherapy was the ability of the patients to retain the donor microbiome. All patients’ microbiomes changed and shifted toward the donors’ post FMT. However, only the responders were able to keep the donor microbiome over time, and the nonresponders’ microbiomes reverted to the previous microbiome,” Dr. Maleki said.
The researchers also conducted a mouse version of the clinical trial. They transplanted mice with the baseline fecal samples of a human responder and then exposed the animals to tumors. They then conducted a second FMT with stool from the human donor, and the animals then responded to anti–PD-1 therapy. The results further confirm “that the donor still has the capacity to drive response in this setting,” Dr. Maleki said.
Dr. Maleki is a board member of IMV Inc.
, defined as complete response, partial response, or stable disease that lasted 6 months or longer. The results come from a small, single arm phase 1 study whose primary endpoint was safety.
“We know that the gut microbiome has shown the ability to affect the systemic antitumor immunity by affecting the CD8+ T cells and CD4+ T cells, and these are the cells that are ultimately important for the function of checkpoint inhibitors. There is now clinical evidence that has shown that changing patient microbiota via fecal microbiota transplantation using stool from previous responder patients has the capacity to sensitize immunotherapy refractory melanomas to anti–PD-1 therapy, (with) about 30% response in this setting,” said Saman Maleki, PhD, during his presentation of the results at the Society for Immunotherapy of Cancer’s 37th Annual Meeting. He also noted that broad-spectrum antibiotics have been shown to negatively influence responses to immunotherapy.
Rather than using stool from donors who responded to immunotherapy, the researchers chose instead to use stool from healthy donors.
The study included 20 patients with advanced melanoma who had not been treated with anti–PD-1 therapy. The median age was 75.5 years, 40% were female, and 75% had wild type BRAF. All patients underwent bowel prep and then received fecal transplants from healthy donors, followed by a 7-day engraftment period before initiating anti–PD-1 therapy in the form of nivolumab or pembrolizumab.
The primary endpoint of the study was safety, and no grade 3 or 4 toxicities were observed during the FMT, and safety signals associated with anti–PD-1 therapies were in line with previous experience.
Fifteen percent of patients had a complete response, 50% had a partial response, 15% had stable disease, and 20% had progressive disease. Seventy-five percent of patients had a complete response, partial response, or stable disease that lasted at least 6 months.
Analysis of the microbiomes showed much higher diversity in the donor microbiomes than in patients. “What was really interesting was that the success of engraftment and retention of the donor microbiome was really key in determining between responders and nonresponders. Responders had successful engraftment that lasted over time, and in nonresponders we did not see that,” said Dr. Maleki, who is a cancer immunology researcher at the University of Western Ontario, London.
They also saw differences between responders and nonresponders in how their microbiome evolved over time. Responders had enrichment in Ruminococcus callidus and other bacteria, while nonresponders had enrichment in different bacteria, among them Catabacter hongkongensis, which has previously been implicated as negatively impacting anti–PD-1 responses, according to Dr. Maleki.
Microbiomes from healthy donors had greater diversity than the patients. Following FMT, patients’ microbiomes increased regardless of clinical response to immunotherapy. However, the tendency for patients to trend toward and retain greater diversity over time was associated with treatment success. “What we saw that was key in patients’ response to immunotherapy was the ability of the patients to retain the donor microbiome. All patients’ microbiomes changed and shifted toward the donors’ post FMT. However, only the responders were able to keep the donor microbiome over time, and the nonresponders’ microbiomes reverted to the previous microbiome,” Dr. Maleki said.
The researchers also conducted a mouse version of the clinical trial. They transplanted mice with the baseline fecal samples of a human responder and then exposed the animals to tumors. They then conducted a second FMT with stool from the human donor, and the animals then responded to anti–PD-1 therapy. The results further confirm “that the donor still has the capacity to drive response in this setting,” Dr. Maleki said.
Dr. Maleki is a board member of IMV Inc.
FROM SITC 2022
New algorithm for large nonpedunculated rectal polyps
Large nonpedunculated rectal polyps (LNPRPs), defined as 20 mm or larger, are associated with a high risk of submucosal invasive cancer (SMIC). Although LNPRPs can be removed by distal colorectal surgery, this approach has an increased risk of morbidity, mortality, and permanent ostomy formation.
The first-line resection technique for LNPRPs is endoscopic mucosal resection (EMR); however, for larger lesions, piecemeal removal is required. When SMIC is revealed after piecemeal resection, surgery is generally recommended, since this is the only way to determine if R0 margins and curative oncologic resection have been achieved.
In such cases, an alternative is endoscopic submucosal dissection (ESD), but there is no current algorithm to choose between the two procedures based on lesion identity.
Optical methods can determine a lesion’s pit and microvascular pattern in real time to determine if SMIC is present, but the performance is modest. Researchers sought to bolster optical detection by combining it with SMIC risk stratification to streamline the choice between EMR and ESD for LNPRPs.
In a study published online in Clinical Gastroenterology and Hepatology, researchers led by Neal Shahidi, MD, of the division of gastroenterology, St. Paul’s Hospital, Vancouver, described a selective resection algorithm (SRA) that could assist gastroenterologists in determining the best procedure to use when confronted with an LNPRP.
“Cost-effectiveness analyses have shown that an SRA using EMR and ESD is the optimal approach. However, a mechanism to facilitate modality selection has not been delineated. To our knowledge, this study is the first to show that a rectum-specific SRA, based on real-time optical evaluation and covert SMIC risk stratification, increases the frequency of curative oncologic resection and minimizes the risk of piecemeal resection of malignant LNPRPs. ... Piecemeal resection of endoscopically curable malignant LNPRPs negates the very benefit that they are intended to provide. the authors wrote.
The researchers conducted a prospective observational study of 480 LNPRPs that were detected between July 2008 and April 2021. They compared the performance of the SRA to that of a universal EMR algorithm (UEA) for procedure determination. The SRA flagged LNPRPs with features consistent with SMIC (< 1,000 mm or Kudo pit pattern Vi) for endoscopic dissection. The latter included Paris 0-Is or 0-IIa+Is nongranular, or 0-IIa+Is granular with a dominant nodule 10 mm or larger. Other LNPRPs were designated to undergo EMR.
The median patient age was 67 years, and 54.2% were men; 90.1% of participants were ASA I-II; 290 LNPRPs were evaluated with the UEA and 190 with the SRA. The median lesion size was 40 mm. Overall, 11.7% of LPNRPs were identified as containing SMIC.
In the SRA, only 1.0% of LNPRPs removed by EMR contained SMIC, while the UEA identified cancer in 12.1%, a significant difference (P = .001). The SRA led to 33.3% as curative oncologic resections, while the UEA achieved only 5.7% (P = .010).
There were no significant differences in technical success or adverse events between the two algorithms.
Procedures determined by SRA took longer than those decided by UEA (median resection duration, 45 vs. 29 minutes; P < .001). Among LNPRPs that were removed through EMR and margin thermal ablation, there was no significant difference in recurrence whether SRA or UEA was used to determine the procedure.
Compared with UEA, SRA was associated with higher rates of en bloc resection (90.5% vs. 11.4%; P < .001), R0 resection (85.7% vs. 5.7%; P < .001), and curative oncologic resection (33.3% vs. 5.7%; P = .010).
“In this study, using analogous optical evaluation and covert SMIC risk stratification criteria, only one (1.0%) [of] malignant LNPRP underwent piecemeal resection within the SRA. This is a pivotal advance in the application of minimally invasive endoscopic resection techniques. It demonstrates an effective approach to optical evaluation; thereby, delineating which LNPRPs can be effectively, efficiently, and safely managed by EMR, compared with those which may derive benefit from ESD,” the authors wrote.
The authors recommended ESD only be used for lesions with suspected superficial SMIC or when there is a heightened risk of SMIC.
A key finding of the study is the frequency of curative resection following ESD. “At 33.3%, this represents a critical improvement in patient outcomes and the application of minimally invasive endoscopic resection techniques; especially when taking into consideration the potential negative ramifications of distal colorectal surgery and evidence showing that endoscopic resection does not impair subsequent surgical intervention,” the authors wrote.
There was no significant difference in recurrence at surveillance colonoscopy between SRA and UEA when undergoing margin thermal ablation. The finding suggests that margin thermal ablation should be considered a vital component of EMR, according to the authors.
Dr. Shahidi received speaker honorarium from Boston Scientific and Pharmascience, and one coauthor received research support from Olympus, Cook Medical, and Boston Scientific.
In clinical practice there is widespread variation in the utilization of endoscopic submucosal dissection (ESD) versus endoscopic mucosal resection (EMR) for resection of large nonpedunculated rectal polyps (LNPRPs).
EMR is easier to learn and faster to perform than ESD and results in fewer perforations. EMR for LNPRPs is usually performed piecemeal, as opposed to ESD in which the goal is en bloc resection. When apparently successful piecemeal EMR is followed by cancer in the pathology report, surgical resection is frequently recommended. This is because assessment of residual cancer risk in the bowel wall or lymph nodes is often considered unachievable after piecemeal resection. Conversely, patients with superficial submucosal invasion after ESD may avoid surgical resection.
This study describes a selective approach to colorectal ESD based on two factors. First, consider ESD primarily in the rectum where the morbidity of surgical resection is highest. Second, consider ESD for those rectal lesions where the cancer risk is highest, including lesions with surface pit and vascular patterns indicating high cancer risk and those with a sessile or nodular component. When this policy was used, only 1% of rectal EMRs were followed by a diagnosis of submucosally invasive cancer. This selective approach to colorectal ESD seems a reasonable combination of procedural efficiency and optimal patient outcomes.
Douglas K. Rex, M.D., MACP, MACG, MASGE, AGAF, is distinguished professor emeritus of medicine, Indiana University, Indianapolis. He serves as a consultant to Olympus Corporation, Boston Scientific, Aries Pharmaceutical, Braintree Laboratories, Lumendi, Norgine, Endokey, GI Supply, Medtronic, and Acacia Pharmaceuticals. He has received research support from EndoAid, Olympus Corporation, Medivators, Erbe USA, Braintree Laboratories and is a shareholder in Satisfai Health.
In clinical practice there is widespread variation in the utilization of endoscopic submucosal dissection (ESD) versus endoscopic mucosal resection (EMR) for resection of large nonpedunculated rectal polyps (LNPRPs).
EMR is easier to learn and faster to perform than ESD and results in fewer perforations. EMR for LNPRPs is usually performed piecemeal, as opposed to ESD in which the goal is en bloc resection. When apparently successful piecemeal EMR is followed by cancer in the pathology report, surgical resection is frequently recommended. This is because assessment of residual cancer risk in the bowel wall or lymph nodes is often considered unachievable after piecemeal resection. Conversely, patients with superficial submucosal invasion after ESD may avoid surgical resection.
This study describes a selective approach to colorectal ESD based on two factors. First, consider ESD primarily in the rectum where the morbidity of surgical resection is highest. Second, consider ESD for those rectal lesions where the cancer risk is highest, including lesions with surface pit and vascular patterns indicating high cancer risk and those with a sessile or nodular component. When this policy was used, only 1% of rectal EMRs were followed by a diagnosis of submucosally invasive cancer. This selective approach to colorectal ESD seems a reasonable combination of procedural efficiency and optimal patient outcomes.
Douglas K. Rex, M.D., MACP, MACG, MASGE, AGAF, is distinguished professor emeritus of medicine, Indiana University, Indianapolis. He serves as a consultant to Olympus Corporation, Boston Scientific, Aries Pharmaceutical, Braintree Laboratories, Lumendi, Norgine, Endokey, GI Supply, Medtronic, and Acacia Pharmaceuticals. He has received research support from EndoAid, Olympus Corporation, Medivators, Erbe USA, Braintree Laboratories and is a shareholder in Satisfai Health.
In clinical practice there is widespread variation in the utilization of endoscopic submucosal dissection (ESD) versus endoscopic mucosal resection (EMR) for resection of large nonpedunculated rectal polyps (LNPRPs).
EMR is easier to learn and faster to perform than ESD and results in fewer perforations. EMR for LNPRPs is usually performed piecemeal, as opposed to ESD in which the goal is en bloc resection. When apparently successful piecemeal EMR is followed by cancer in the pathology report, surgical resection is frequently recommended. This is because assessment of residual cancer risk in the bowel wall or lymph nodes is often considered unachievable after piecemeal resection. Conversely, patients with superficial submucosal invasion after ESD may avoid surgical resection.
This study describes a selective approach to colorectal ESD based on two factors. First, consider ESD primarily in the rectum where the morbidity of surgical resection is highest. Second, consider ESD for those rectal lesions where the cancer risk is highest, including lesions with surface pit and vascular patterns indicating high cancer risk and those with a sessile or nodular component. When this policy was used, only 1% of rectal EMRs were followed by a diagnosis of submucosally invasive cancer. This selective approach to colorectal ESD seems a reasonable combination of procedural efficiency and optimal patient outcomes.
Douglas K. Rex, M.D., MACP, MACG, MASGE, AGAF, is distinguished professor emeritus of medicine, Indiana University, Indianapolis. He serves as a consultant to Olympus Corporation, Boston Scientific, Aries Pharmaceutical, Braintree Laboratories, Lumendi, Norgine, Endokey, GI Supply, Medtronic, and Acacia Pharmaceuticals. He has received research support from EndoAid, Olympus Corporation, Medivators, Erbe USA, Braintree Laboratories and is a shareholder in Satisfai Health.
Large nonpedunculated rectal polyps (LNPRPs), defined as 20 mm or larger, are associated with a high risk of submucosal invasive cancer (SMIC). Although LNPRPs can be removed by distal colorectal surgery, this approach has an increased risk of morbidity, mortality, and permanent ostomy formation.
The first-line resection technique for LNPRPs is endoscopic mucosal resection (EMR); however, for larger lesions, piecemeal removal is required. When SMIC is revealed after piecemeal resection, surgery is generally recommended, since this is the only way to determine if R0 margins and curative oncologic resection have been achieved.
In such cases, an alternative is endoscopic submucosal dissection (ESD), but there is no current algorithm to choose between the two procedures based on lesion identity.
Optical methods can determine a lesion’s pit and microvascular pattern in real time to determine if SMIC is present, but the performance is modest. Researchers sought to bolster optical detection by combining it with SMIC risk stratification to streamline the choice between EMR and ESD for LNPRPs.
In a study published online in Clinical Gastroenterology and Hepatology, researchers led by Neal Shahidi, MD, of the division of gastroenterology, St. Paul’s Hospital, Vancouver, described a selective resection algorithm (SRA) that could assist gastroenterologists in determining the best procedure to use when confronted with an LNPRP.
“Cost-effectiveness analyses have shown that an SRA using EMR and ESD is the optimal approach. However, a mechanism to facilitate modality selection has not been delineated. To our knowledge, this study is the first to show that a rectum-specific SRA, based on real-time optical evaluation and covert SMIC risk stratification, increases the frequency of curative oncologic resection and minimizes the risk of piecemeal resection of malignant LNPRPs. ... Piecemeal resection of endoscopically curable malignant LNPRPs negates the very benefit that they are intended to provide. the authors wrote.
The researchers conducted a prospective observational study of 480 LNPRPs that were detected between July 2008 and April 2021. They compared the performance of the SRA to that of a universal EMR algorithm (UEA) for procedure determination. The SRA flagged LNPRPs with features consistent with SMIC (< 1,000 mm or Kudo pit pattern Vi) for endoscopic dissection. The latter included Paris 0-Is or 0-IIa+Is nongranular, or 0-IIa+Is granular with a dominant nodule 10 mm or larger. Other LNPRPs were designated to undergo EMR.
The median patient age was 67 years, and 54.2% were men; 90.1% of participants were ASA I-II; 290 LNPRPs were evaluated with the UEA and 190 with the SRA. The median lesion size was 40 mm. Overall, 11.7% of LPNRPs were identified as containing SMIC.
In the SRA, only 1.0% of LNPRPs removed by EMR contained SMIC, while the UEA identified cancer in 12.1%, a significant difference (P = .001). The SRA led to 33.3% as curative oncologic resections, while the UEA achieved only 5.7% (P = .010).
There were no significant differences in technical success or adverse events between the two algorithms.
Procedures determined by SRA took longer than those decided by UEA (median resection duration, 45 vs. 29 minutes; P < .001). Among LNPRPs that were removed through EMR and margin thermal ablation, there was no significant difference in recurrence whether SRA or UEA was used to determine the procedure.
Compared with UEA, SRA was associated with higher rates of en bloc resection (90.5% vs. 11.4%; P < .001), R0 resection (85.7% vs. 5.7%; P < .001), and curative oncologic resection (33.3% vs. 5.7%; P = .010).
“In this study, using analogous optical evaluation and covert SMIC risk stratification criteria, only one (1.0%) [of] malignant LNPRP underwent piecemeal resection within the SRA. This is a pivotal advance in the application of minimally invasive endoscopic resection techniques. It demonstrates an effective approach to optical evaluation; thereby, delineating which LNPRPs can be effectively, efficiently, and safely managed by EMR, compared with those which may derive benefit from ESD,” the authors wrote.
The authors recommended ESD only be used for lesions with suspected superficial SMIC or when there is a heightened risk of SMIC.
A key finding of the study is the frequency of curative resection following ESD. “At 33.3%, this represents a critical improvement in patient outcomes and the application of minimally invasive endoscopic resection techniques; especially when taking into consideration the potential negative ramifications of distal colorectal surgery and evidence showing that endoscopic resection does not impair subsequent surgical intervention,” the authors wrote.
There was no significant difference in recurrence at surveillance colonoscopy between SRA and UEA when undergoing margin thermal ablation. The finding suggests that margin thermal ablation should be considered a vital component of EMR, according to the authors.
Dr. Shahidi received speaker honorarium from Boston Scientific and Pharmascience, and one coauthor received research support from Olympus, Cook Medical, and Boston Scientific.
Large nonpedunculated rectal polyps (LNPRPs), defined as 20 mm or larger, are associated with a high risk of submucosal invasive cancer (SMIC). Although LNPRPs can be removed by distal colorectal surgery, this approach has an increased risk of morbidity, mortality, and permanent ostomy formation.
The first-line resection technique for LNPRPs is endoscopic mucosal resection (EMR); however, for larger lesions, piecemeal removal is required. When SMIC is revealed after piecemeal resection, surgery is generally recommended, since this is the only way to determine if R0 margins and curative oncologic resection have been achieved.
In such cases, an alternative is endoscopic submucosal dissection (ESD), but there is no current algorithm to choose between the two procedures based on lesion identity.
Optical methods can determine a lesion’s pit and microvascular pattern in real time to determine if SMIC is present, but the performance is modest. Researchers sought to bolster optical detection by combining it with SMIC risk stratification to streamline the choice between EMR and ESD for LNPRPs.
In a study published online in Clinical Gastroenterology and Hepatology, researchers led by Neal Shahidi, MD, of the division of gastroenterology, St. Paul’s Hospital, Vancouver, described a selective resection algorithm (SRA) that could assist gastroenterologists in determining the best procedure to use when confronted with an LNPRP.
“Cost-effectiveness analyses have shown that an SRA using EMR and ESD is the optimal approach. However, a mechanism to facilitate modality selection has not been delineated. To our knowledge, this study is the first to show that a rectum-specific SRA, based on real-time optical evaluation and covert SMIC risk stratification, increases the frequency of curative oncologic resection and minimizes the risk of piecemeal resection of malignant LNPRPs. ... Piecemeal resection of endoscopically curable malignant LNPRPs negates the very benefit that they are intended to provide. the authors wrote.
The researchers conducted a prospective observational study of 480 LNPRPs that were detected between July 2008 and April 2021. They compared the performance of the SRA to that of a universal EMR algorithm (UEA) for procedure determination. The SRA flagged LNPRPs with features consistent with SMIC (< 1,000 mm or Kudo pit pattern Vi) for endoscopic dissection. The latter included Paris 0-Is or 0-IIa+Is nongranular, or 0-IIa+Is granular with a dominant nodule 10 mm or larger. Other LNPRPs were designated to undergo EMR.
The median patient age was 67 years, and 54.2% were men; 90.1% of participants were ASA I-II; 290 LNPRPs were evaluated with the UEA and 190 with the SRA. The median lesion size was 40 mm. Overall, 11.7% of LPNRPs were identified as containing SMIC.
In the SRA, only 1.0% of LNPRPs removed by EMR contained SMIC, while the UEA identified cancer in 12.1%, a significant difference (P = .001). The SRA led to 33.3% as curative oncologic resections, while the UEA achieved only 5.7% (P = .010).
There were no significant differences in technical success or adverse events between the two algorithms.
Procedures determined by SRA took longer than those decided by UEA (median resection duration, 45 vs. 29 minutes; P < .001). Among LNPRPs that were removed through EMR and margin thermal ablation, there was no significant difference in recurrence whether SRA or UEA was used to determine the procedure.
Compared with UEA, SRA was associated with higher rates of en bloc resection (90.5% vs. 11.4%; P < .001), R0 resection (85.7% vs. 5.7%; P < .001), and curative oncologic resection (33.3% vs. 5.7%; P = .010).
“In this study, using analogous optical evaluation and covert SMIC risk stratification criteria, only one (1.0%) [of] malignant LNPRP underwent piecemeal resection within the SRA. This is a pivotal advance in the application of minimally invasive endoscopic resection techniques. It demonstrates an effective approach to optical evaluation; thereby, delineating which LNPRPs can be effectively, efficiently, and safely managed by EMR, compared with those which may derive benefit from ESD,” the authors wrote.
The authors recommended ESD only be used for lesions with suspected superficial SMIC or when there is a heightened risk of SMIC.
A key finding of the study is the frequency of curative resection following ESD. “At 33.3%, this represents a critical improvement in patient outcomes and the application of minimally invasive endoscopic resection techniques; especially when taking into consideration the potential negative ramifications of distal colorectal surgery and evidence showing that endoscopic resection does not impair subsequent surgical intervention,” the authors wrote.
There was no significant difference in recurrence at surveillance colonoscopy between SRA and UEA when undergoing margin thermal ablation. The finding suggests that margin thermal ablation should be considered a vital component of EMR, according to the authors.
Dr. Shahidi received speaker honorarium from Boston Scientific and Pharmascience, and one coauthor received research support from Olympus, Cook Medical, and Boston Scientific.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Consider gaps in access and knowledge in diagnosis and treatment in skin of color
LAS VEGAS – and patients, Susan C. Taylor, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.
Additionally, some disparities occur because of gaps in access to health care, said Dr. Taylor, vice chair, diversity, equity and inclusion, in the department of dermatology at the University of Pennsylvania, Philadelphia, who moderated an expert panel discussion of treatment tips for several common dermatologic conditions in skin of color patients.
Atopic dermatitis angles
Atopic dermatitis (AD) is the fourth most common dermatologic complaint in Black patients, based on data from the United States National Ambulatory Medical Care Survey. Also, data from the National Health and Nutrition Examination Survey show that Black children are nearly twice as likely as White children to develop AD after controlling for socioeconomic factors, Dr. Taylor said.
When Black patients present with AD, “you may not see the erythema,” said Valerie D. Callender, MD, of Howard University, Washington, who presented on AD. Instead, “you may see more follicular and papular presentations.” Erythema and erythroderma can present as shades of violet, gray, or dark brown in patients with rich skin tones, added Dr. Callender, who practices in Glenn Dale, Md.
Consequently, disease severity can be misinterpreted, she said, noting that data suggest that scoring systems such as the Eczema Area and Severity Index and Scoring Atopic Dermatitis underestimate AD severity in dark skin.
As for treatment, skin of color patients with AD are often as bothered by postinflammatory hyperpigmentation (PIH) as by active lesions, so treatment should take these concerns into account, Dr. Callender said. Studies evaluating the effectiveness of AD treatments in diverse populations are limited by lack of representation of racial groups in clinical trials and lack of subset analyses by race.
Acne awareness
An important consideration of acne in skin of color patients is that the acne “might not be red, it might just be darker,” said Andrew F. Alexis, MD, vice-chair for diversity and inclusion in the department of dermatology, and professor of clinical dermatology at Weill Cornell Medicine, New York. A study published in JAMA Dermatology of nearly 30,000 patients with acne from 2007 to 2017 found that non-Hispanic Black patients were more likely than non-Hispanic White patients to see a dermatologist for acne, but Black patients received fewer prescriptions for acne medications than White patients.
The study also showed that Black patients who received prescriptions for acne were more likely to receive topical retinoids and topical antibiotics, and less likely to receive oral antibiotics, spironolactone, or isotretinoin, compared with White patients. Similarly, Asian patients were more likely to receive topical antibiotics and less likely to receive oral antibiotics, compared with White patients.
Other panelists shared some of their best practices for acne in patients with skin of color, including treatment with topical retinoids (for inflammation) and spironolactone, and therapies that address both inflammation and pigmentation, such as salicylic acid and azelaic acid. Dr. Callender also advised asking patients about makeup, as they may not know that many types of makeup used to cover acne are in fact comedogenic.
Melanoma misconceptions
One of the most common misperceptions about melanoma among skin of color patients is that they don’t think they can get it, Dr. Taylor said. Many health care providers don’t think about melanoma in skin of color patients because of the dramatically lower incidence in this population, but as a result, cases may go undiagnosed, and as studies have shown, the mortality rate from melanoma is higher in Black patients.
Consider the palms, soles, nails, and web spaces as possible melanoma sites, Dr. Taylor added.
Educating skin of color patients about melanoma is important, although the incidence is 20 to 30 times lower than in non-Hispanic Whites, said Nada Elbuluk, MD, the founder and director of the University of Southern California Skin of Color Center and Pigmentary Disorders Clinic, Los Angeles. A 2020 editorial published in Cancer Cytopathology pointed out that 1 in 3 Black men or women with a melanoma diagnosis in the United States dies of the disease, compared with 1 in 7 non-Hispanic White men and 1 in 11 non-Hispanic White women with melanoma.
Don’t skip the total body skin exam in these patients, Dr. Elbuluk emphasized. Many patients will only partially undress, and areas such as toes can be missed.
Rosacea review
For patients with skin of color, clinicians need to look for different signs of rosacea than those typically seen in White patients, Dr. Elbuluk said. “The most common presentation of rosacea in skin of color is papulopustular,” and the granulomatous variant.
“These patients will often give you a history of sensitivity to products,” Dr. Elbuluk noted. They may not always have the flushing, but they may report warmth or itching, in addition to product sensitivity.
When considering rosacea in skin of color patients, be sure to have good lighting for close examination, as skin thickening is another subtle sign of rosacea in these patients, she said. Skin thickening “is a very early sign that will present in skin of color with no erythema, so keep that in mind.”
Stinging and burning sensations may be reported by skin of color patients with rosacea. Use patient history to confirm the diagnosis of rosacea, which is often delayed in skin of color patients because of a low index of suspicion, she said.
Psoriasis pointers
Psoriasis in skin of color patients used to be considered rare, “but that is far from true,” Dr. Alexis said. In fact, many cases of psoriasis are undiagnosed or the diagnosis is delayed in these patients.
The panelists noted that current guidelines for psoriasis treatment are based on clinical trials composed mainly of White patients, and do not contain specific recommendations for skin of color patients.
Notably, the morphology, location, and color of psoriasis lesions may be different for patients with darker skin, such as thicker plaques and more scaling over larger areas, they said. Also, skin of color patients may experience long-lasting dyspigmentation from psoriasis lesions that have resolved.
When developing a strategy for psoriasis in skin of color patients, consider not only disease severity, but also comorbidities and medications, response (if any) to prior therapies, patient preferences, and quality of life, the panelists said.
Dr. Callender, Dr. Elbuluk, Dr. Taylor, and Dr. Alexis reported conflicts of interest from numerous sources in industry. MedscapeLive and this news organization are owned by the same parent company.
LAS VEGAS – and patients, Susan C. Taylor, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.
Additionally, some disparities occur because of gaps in access to health care, said Dr. Taylor, vice chair, diversity, equity and inclusion, in the department of dermatology at the University of Pennsylvania, Philadelphia, who moderated an expert panel discussion of treatment tips for several common dermatologic conditions in skin of color patients.
Atopic dermatitis angles
Atopic dermatitis (AD) is the fourth most common dermatologic complaint in Black patients, based on data from the United States National Ambulatory Medical Care Survey. Also, data from the National Health and Nutrition Examination Survey show that Black children are nearly twice as likely as White children to develop AD after controlling for socioeconomic factors, Dr. Taylor said.
When Black patients present with AD, “you may not see the erythema,” said Valerie D. Callender, MD, of Howard University, Washington, who presented on AD. Instead, “you may see more follicular and papular presentations.” Erythema and erythroderma can present as shades of violet, gray, or dark brown in patients with rich skin tones, added Dr. Callender, who practices in Glenn Dale, Md.
Consequently, disease severity can be misinterpreted, she said, noting that data suggest that scoring systems such as the Eczema Area and Severity Index and Scoring Atopic Dermatitis underestimate AD severity in dark skin.
As for treatment, skin of color patients with AD are often as bothered by postinflammatory hyperpigmentation (PIH) as by active lesions, so treatment should take these concerns into account, Dr. Callender said. Studies evaluating the effectiveness of AD treatments in diverse populations are limited by lack of representation of racial groups in clinical trials and lack of subset analyses by race.
Acne awareness
An important consideration of acne in skin of color patients is that the acne “might not be red, it might just be darker,” said Andrew F. Alexis, MD, vice-chair for diversity and inclusion in the department of dermatology, and professor of clinical dermatology at Weill Cornell Medicine, New York. A study published in JAMA Dermatology of nearly 30,000 patients with acne from 2007 to 2017 found that non-Hispanic Black patients were more likely than non-Hispanic White patients to see a dermatologist for acne, but Black patients received fewer prescriptions for acne medications than White patients.
The study also showed that Black patients who received prescriptions for acne were more likely to receive topical retinoids and topical antibiotics, and less likely to receive oral antibiotics, spironolactone, or isotretinoin, compared with White patients. Similarly, Asian patients were more likely to receive topical antibiotics and less likely to receive oral antibiotics, compared with White patients.
Other panelists shared some of their best practices for acne in patients with skin of color, including treatment with topical retinoids (for inflammation) and spironolactone, and therapies that address both inflammation and pigmentation, such as salicylic acid and azelaic acid. Dr. Callender also advised asking patients about makeup, as they may not know that many types of makeup used to cover acne are in fact comedogenic.
Melanoma misconceptions
One of the most common misperceptions about melanoma among skin of color patients is that they don’t think they can get it, Dr. Taylor said. Many health care providers don’t think about melanoma in skin of color patients because of the dramatically lower incidence in this population, but as a result, cases may go undiagnosed, and as studies have shown, the mortality rate from melanoma is higher in Black patients.
Consider the palms, soles, nails, and web spaces as possible melanoma sites, Dr. Taylor added.
Educating skin of color patients about melanoma is important, although the incidence is 20 to 30 times lower than in non-Hispanic Whites, said Nada Elbuluk, MD, the founder and director of the University of Southern California Skin of Color Center and Pigmentary Disorders Clinic, Los Angeles. A 2020 editorial published in Cancer Cytopathology pointed out that 1 in 3 Black men or women with a melanoma diagnosis in the United States dies of the disease, compared with 1 in 7 non-Hispanic White men and 1 in 11 non-Hispanic White women with melanoma.
Don’t skip the total body skin exam in these patients, Dr. Elbuluk emphasized. Many patients will only partially undress, and areas such as toes can be missed.
Rosacea review
For patients with skin of color, clinicians need to look for different signs of rosacea than those typically seen in White patients, Dr. Elbuluk said. “The most common presentation of rosacea in skin of color is papulopustular,” and the granulomatous variant.
“These patients will often give you a history of sensitivity to products,” Dr. Elbuluk noted. They may not always have the flushing, but they may report warmth or itching, in addition to product sensitivity.
When considering rosacea in skin of color patients, be sure to have good lighting for close examination, as skin thickening is another subtle sign of rosacea in these patients, she said. Skin thickening “is a very early sign that will present in skin of color with no erythema, so keep that in mind.”
Stinging and burning sensations may be reported by skin of color patients with rosacea. Use patient history to confirm the diagnosis of rosacea, which is often delayed in skin of color patients because of a low index of suspicion, she said.
Psoriasis pointers
Psoriasis in skin of color patients used to be considered rare, “but that is far from true,” Dr. Alexis said. In fact, many cases of psoriasis are undiagnosed or the diagnosis is delayed in these patients.
The panelists noted that current guidelines for psoriasis treatment are based on clinical trials composed mainly of White patients, and do not contain specific recommendations for skin of color patients.
Notably, the morphology, location, and color of psoriasis lesions may be different for patients with darker skin, such as thicker plaques and more scaling over larger areas, they said. Also, skin of color patients may experience long-lasting dyspigmentation from psoriasis lesions that have resolved.
When developing a strategy for psoriasis in skin of color patients, consider not only disease severity, but also comorbidities and medications, response (if any) to prior therapies, patient preferences, and quality of life, the panelists said.
Dr. Callender, Dr. Elbuluk, Dr. Taylor, and Dr. Alexis reported conflicts of interest from numerous sources in industry. MedscapeLive and this news organization are owned by the same parent company.
LAS VEGAS – and patients, Susan C. Taylor, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.
Additionally, some disparities occur because of gaps in access to health care, said Dr. Taylor, vice chair, diversity, equity and inclusion, in the department of dermatology at the University of Pennsylvania, Philadelphia, who moderated an expert panel discussion of treatment tips for several common dermatologic conditions in skin of color patients.
Atopic dermatitis angles
Atopic dermatitis (AD) is the fourth most common dermatologic complaint in Black patients, based on data from the United States National Ambulatory Medical Care Survey. Also, data from the National Health and Nutrition Examination Survey show that Black children are nearly twice as likely as White children to develop AD after controlling for socioeconomic factors, Dr. Taylor said.
When Black patients present with AD, “you may not see the erythema,” said Valerie D. Callender, MD, of Howard University, Washington, who presented on AD. Instead, “you may see more follicular and papular presentations.” Erythema and erythroderma can present as shades of violet, gray, or dark brown in patients with rich skin tones, added Dr. Callender, who practices in Glenn Dale, Md.
Consequently, disease severity can be misinterpreted, she said, noting that data suggest that scoring systems such as the Eczema Area and Severity Index and Scoring Atopic Dermatitis underestimate AD severity in dark skin.
As for treatment, skin of color patients with AD are often as bothered by postinflammatory hyperpigmentation (PIH) as by active lesions, so treatment should take these concerns into account, Dr. Callender said. Studies evaluating the effectiveness of AD treatments in diverse populations are limited by lack of representation of racial groups in clinical trials and lack of subset analyses by race.
Acne awareness
An important consideration of acne in skin of color patients is that the acne “might not be red, it might just be darker,” said Andrew F. Alexis, MD, vice-chair for diversity and inclusion in the department of dermatology, and professor of clinical dermatology at Weill Cornell Medicine, New York. A study published in JAMA Dermatology of nearly 30,000 patients with acne from 2007 to 2017 found that non-Hispanic Black patients were more likely than non-Hispanic White patients to see a dermatologist for acne, but Black patients received fewer prescriptions for acne medications than White patients.
The study also showed that Black patients who received prescriptions for acne were more likely to receive topical retinoids and topical antibiotics, and less likely to receive oral antibiotics, spironolactone, or isotretinoin, compared with White patients. Similarly, Asian patients were more likely to receive topical antibiotics and less likely to receive oral antibiotics, compared with White patients.
Other panelists shared some of their best practices for acne in patients with skin of color, including treatment with topical retinoids (for inflammation) and spironolactone, and therapies that address both inflammation and pigmentation, such as salicylic acid and azelaic acid. Dr. Callender also advised asking patients about makeup, as they may not know that many types of makeup used to cover acne are in fact comedogenic.
Melanoma misconceptions
One of the most common misperceptions about melanoma among skin of color patients is that they don’t think they can get it, Dr. Taylor said. Many health care providers don’t think about melanoma in skin of color patients because of the dramatically lower incidence in this population, but as a result, cases may go undiagnosed, and as studies have shown, the mortality rate from melanoma is higher in Black patients.
Consider the palms, soles, nails, and web spaces as possible melanoma sites, Dr. Taylor added.
Educating skin of color patients about melanoma is important, although the incidence is 20 to 30 times lower than in non-Hispanic Whites, said Nada Elbuluk, MD, the founder and director of the University of Southern California Skin of Color Center and Pigmentary Disorders Clinic, Los Angeles. A 2020 editorial published in Cancer Cytopathology pointed out that 1 in 3 Black men or women with a melanoma diagnosis in the United States dies of the disease, compared with 1 in 7 non-Hispanic White men and 1 in 11 non-Hispanic White women with melanoma.
Don’t skip the total body skin exam in these patients, Dr. Elbuluk emphasized. Many patients will only partially undress, and areas such as toes can be missed.
Rosacea review
For patients with skin of color, clinicians need to look for different signs of rosacea than those typically seen in White patients, Dr. Elbuluk said. “The most common presentation of rosacea in skin of color is papulopustular,” and the granulomatous variant.
“These patients will often give you a history of sensitivity to products,” Dr. Elbuluk noted. They may not always have the flushing, but they may report warmth or itching, in addition to product sensitivity.
When considering rosacea in skin of color patients, be sure to have good lighting for close examination, as skin thickening is another subtle sign of rosacea in these patients, she said. Skin thickening “is a very early sign that will present in skin of color with no erythema, so keep that in mind.”
Stinging and burning sensations may be reported by skin of color patients with rosacea. Use patient history to confirm the diagnosis of rosacea, which is often delayed in skin of color patients because of a low index of suspicion, she said.
Psoriasis pointers
Psoriasis in skin of color patients used to be considered rare, “but that is far from true,” Dr. Alexis said. In fact, many cases of psoriasis are undiagnosed or the diagnosis is delayed in these patients.
The panelists noted that current guidelines for psoriasis treatment are based on clinical trials composed mainly of White patients, and do not contain specific recommendations for skin of color patients.
Notably, the morphology, location, and color of psoriasis lesions may be different for patients with darker skin, such as thicker plaques and more scaling over larger areas, they said. Also, skin of color patients may experience long-lasting dyspigmentation from psoriasis lesions that have resolved.
When developing a strategy for psoriasis in skin of color patients, consider not only disease severity, but also comorbidities and medications, response (if any) to prior therapies, patient preferences, and quality of life, the panelists said.
Dr. Callender, Dr. Elbuluk, Dr. Taylor, and Dr. Alexis reported conflicts of interest from numerous sources in industry. MedscapeLive and this news organization are owned by the same parent company.
AT INNOVATIONS IN DERMATOLOGY
Highlights in Diabetes and Metabolism From ASN 2022
Dr Carol Wysham, of the University of Washington School of Medicine in Spokane, reports on key studies looking at glucose-lowering therapies in adults with type 2 diabetes, as presented at the 2022 annual meeting of the American Society of Nephrology.
Dr Wysham first highlights a real-world study evaluating the long-term use of empagliflozin compared with dipeptidyl peptidase-4 (DPP-4) inhibitors. The researchers used the estimated glomerular filtration rate (eGFR) slope as their predictive value for clinical kidney benefit. They found that long-term use of empagliflozin was associated with less impairment of kidney function than DPP-4 inhibitors.
Next, Dr Wysham discusses a study testing the safety of SGLT2 inhibitors in patients with both chronic kidney disease and type 2 diabetes. Researchers found that in this patient population undergoing routine care, use of SGLT2 inhibitors was associated with an increased risk for nonvertebral fractures, lower-limb amputations, and genital infections.
Next, Dr Wysham examines a report pooling data from the SUSTAIN 6 and PIONEER 6 studies to determine whether semaglutide improves the eGFR slope. Researchers found that across the A1c and blood pressure subgroups, semaglutide reduced eGFR compared with placebo.
Finally, Dr Wysham discusses an analysis using data from the Framingham Heart Study to determine whether a demonstrable link could be established between kidney disease and mild cognitive impairment. Researchers reported that patients with albuminuria had an increased risk for brain infarctions.
--
Carol Wysham, MD, Clinical Professor of Medicine, Department of Medicine, University of Washington School of Medicine; Clinical Endocrinologist, Rockwood Center for Diabetes and Endocrinology, MultiCare Health Systems, Spokane, Washington
Carol Wysham, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Endocrine Society; MultiCare Health Systems
Received research grant from: Allergan; Abbott; Corcept; Eli Lilly; Mylan; Novo Nordisk; Regeneron
Dr Carol Wysham, of the University of Washington School of Medicine in Spokane, reports on key studies looking at glucose-lowering therapies in adults with type 2 diabetes, as presented at the 2022 annual meeting of the American Society of Nephrology.
Dr Wysham first highlights a real-world study evaluating the long-term use of empagliflozin compared with dipeptidyl peptidase-4 (DPP-4) inhibitors. The researchers used the estimated glomerular filtration rate (eGFR) slope as their predictive value for clinical kidney benefit. They found that long-term use of empagliflozin was associated with less impairment of kidney function than DPP-4 inhibitors.
Next, Dr Wysham discusses a study testing the safety of SGLT2 inhibitors in patients with both chronic kidney disease and type 2 diabetes. Researchers found that in this patient population undergoing routine care, use of SGLT2 inhibitors was associated with an increased risk for nonvertebral fractures, lower-limb amputations, and genital infections.
Next, Dr Wysham examines a report pooling data from the SUSTAIN 6 and PIONEER 6 studies to determine whether semaglutide improves the eGFR slope. Researchers found that across the A1c and blood pressure subgroups, semaglutide reduced eGFR compared with placebo.
Finally, Dr Wysham discusses an analysis using data from the Framingham Heart Study to determine whether a demonstrable link could be established between kidney disease and mild cognitive impairment. Researchers reported that patients with albuminuria had an increased risk for brain infarctions.
--
Carol Wysham, MD, Clinical Professor of Medicine, Department of Medicine, University of Washington School of Medicine; Clinical Endocrinologist, Rockwood Center for Diabetes and Endocrinology, MultiCare Health Systems, Spokane, Washington
Carol Wysham, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Endocrine Society; MultiCare Health Systems
Received research grant from: Allergan; Abbott; Corcept; Eli Lilly; Mylan; Novo Nordisk; Regeneron
Dr Carol Wysham, of the University of Washington School of Medicine in Spokane, reports on key studies looking at glucose-lowering therapies in adults with type 2 diabetes, as presented at the 2022 annual meeting of the American Society of Nephrology.
Dr Wysham first highlights a real-world study evaluating the long-term use of empagliflozin compared with dipeptidyl peptidase-4 (DPP-4) inhibitors. The researchers used the estimated glomerular filtration rate (eGFR) slope as their predictive value for clinical kidney benefit. They found that long-term use of empagliflozin was associated with less impairment of kidney function than DPP-4 inhibitors.
Next, Dr Wysham discusses a study testing the safety of SGLT2 inhibitors in patients with both chronic kidney disease and type 2 diabetes. Researchers found that in this patient population undergoing routine care, use of SGLT2 inhibitors was associated with an increased risk for nonvertebral fractures, lower-limb amputations, and genital infections.
Next, Dr Wysham examines a report pooling data from the SUSTAIN 6 and PIONEER 6 studies to determine whether semaglutide improves the eGFR slope. Researchers found that across the A1c and blood pressure subgroups, semaglutide reduced eGFR compared with placebo.
Finally, Dr Wysham discusses an analysis using data from the Framingham Heart Study to determine whether a demonstrable link could be established between kidney disease and mild cognitive impairment. Researchers reported that patients with albuminuria had an increased risk for brain infarctions.
--
Carol Wysham, MD, Clinical Professor of Medicine, Department of Medicine, University of Washington School of Medicine; Clinical Endocrinologist, Rockwood Center for Diabetes and Endocrinology, MultiCare Health Systems, Spokane, Washington
Carol Wysham, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Endocrine Society; MultiCare Health Systems
Received research grant from: Allergan; Abbott; Corcept; Eli Lilly; Mylan; Novo Nordisk; Regeneron
Skinny-label biosimilars provide substantial savings to Medicare
Recent court rulings could put such saving under threat
Competition between five biologic drugs and their skinny-label biosimilars saved Medicare an estimated $1.5 billion during 2015-2020. But these savings accruing to Medicare and the availability of those and other biosimilars through skinny labeling is under threat from recent court rulings, according to a research letter published online in JAMA Internal Medicine.
The authors highlighted the need for such savings by noting that, while biologics comprise less than 5% of prescription drug use, their price tag amounts to about 40% of U.S. drug spending, Biologic manufacturers often delay the availability of biosimilars for additional years beyond the original patent expiration through further patents for supplemental indications. To provide a counterbalance, federal law allows the Food and Drug Administration to approve “skinny-label” generics and biosimilars that carve out patent-protected indications or regulatory exclusivities. But once a generic drug reaches the market through this process with a skinny label, it may often be substituted for indications that go beyond the ones listed on the skinny label. In fact, some state laws mandate that pharmacists substitute interchangeable generics for brand-name drugs, helping to decrease drug prices. In response to legal threats to the skinny-label pathway, Alexander C. Egilman and colleagues at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, assessed the frequency of approval and marketing of skinny-label biosimilars from 2015 to 2021 and the resultant savings to Medicare.
The authors estimated annual Part B (clinician-administered) savings from skinny-label biosimilars through 2020 by comparing actual biologic and skinny-label biosimilar spending with estimated biologic spending without competition using the Medicare Dashboard. They assumed that the unit price of the biologic would increase at its 5-year compound annual growth rate prior to competition.
In that period, the FDA approved 33 biosimilars linked to 11 biologics. Among them, 22 (66.7%) had a skinny label. Of 21 biosimilars marketed before 2022, 13 (61.9%) were launched with a skinny label. Of the 8 biologics linked to these 21 biosimilars, 5 of the first-to-market biosimilars had skinny labels (bevacizumab, filgrastim, infliximab, pegfilgrastim, and rituximab), leading to earlier competition through 2021.
The estimated $1.5 billion in savings to Medicare from these skinny-label biosimilars over the 2015-2020 span represents 4.9% of the $30.2 billion that Medicare spent on the five biologics during this period. The researchers pointed out that once adalimumab (Humira) faces skinny-label biosimilar competition in 2023, savings will likely grow substantially.
In response to the research letter, an editor’s note by JAMA Internal Medicine Editorial Fellow Eric Ward, MD, and JAMA Internal Medicine Editor at Large and Online Editor Robert Steinbrook, MD, stated that, between 2015 and 2019, 24 (43%) of 56 brand-name drugs had competition from skinny-labeled generic formulations after first becoming available as generics.
The editors also referenced a JAMA Viewpoints article from 2021 that reviewed the most recent case challenging the skinny-label pathway in which GlaxoSmithKline sued Teva for its marketing of a skinny-label generic of the brand-name beta-blocker carvedilol (Coreg) that the plaintive claimed “induced physicians to prescribe carvedilol for indications that had been carved out by Teva’s skinny label, thus infringing GlaxoSmithKline’s patents.” A $235 million judgment against Teva was overturned by a district court and then reversed again by a Federal Circuit court that, after receiving criticism, reconsidered the case, and a panel affirmed the judgment against Teva.
“The Federal Circuit panel’s decision has the potential to put generic drugs that fail to adequately carve out indications from the brand name labeling at risk for damages related to infringement,” the authors wrote. Similar claims of infringement are being heard in other courts, they wrote, and they urged careful targeting of skinny-label carveouts, and suggest also that challenges to the arguments used against Teva focus on preservation of First Amendment rights as protection for lawful and accurate speech in drug labels.
“The legal uncertainties are likely to continue, as manufacturers pursue novel and complex strategies to protect the patents and regulatory exclusivities of brand-name drugs and biologics,” Dr. Ward and Dr. Steinbrook wrote, adding that “the path forward is for Congress to enact additional legislation that reaffirms and strengthens the permissibility of skinny labeling.”
The research letter’s corresponding author, Ameet Sarpatwari, PhD, JD, assistant professor at Harvard Medical School, and assistant director for the Harvard Program On Regulation, Therapeutics, And Law, echoed concerns over the Teva case in an interview. “There has certainly been concern that should the appellate decision stand, there will be a chilling effect. As the lone dissenter in that case noted, ‘no skinny-label generic is safe.’ I think many generic and biosimilar manufacturers are awaiting to see whether the Supreme Court will take the case.”
He added: “I do not believe the likelihood of skinny-label-supportive legislation making it through Congress will be greatly diminished in a divided Congress. Democrats and Republicans alike should seek to promote competition in the marketplace, which is what the skinny-labeling pathway accomplishes.”
The authors reported no relevant conflicts of interest. The research was funded by a grant from Arnold Ventures.
Recent court rulings could put such saving under threat
Recent court rulings could put such saving under threat
Competition between five biologic drugs and their skinny-label biosimilars saved Medicare an estimated $1.5 billion during 2015-2020. But these savings accruing to Medicare and the availability of those and other biosimilars through skinny labeling is under threat from recent court rulings, according to a research letter published online in JAMA Internal Medicine.
The authors highlighted the need for such savings by noting that, while biologics comprise less than 5% of prescription drug use, their price tag amounts to about 40% of U.S. drug spending, Biologic manufacturers often delay the availability of biosimilars for additional years beyond the original patent expiration through further patents for supplemental indications. To provide a counterbalance, federal law allows the Food and Drug Administration to approve “skinny-label” generics and biosimilars that carve out patent-protected indications or regulatory exclusivities. But once a generic drug reaches the market through this process with a skinny label, it may often be substituted for indications that go beyond the ones listed on the skinny label. In fact, some state laws mandate that pharmacists substitute interchangeable generics for brand-name drugs, helping to decrease drug prices. In response to legal threats to the skinny-label pathway, Alexander C. Egilman and colleagues at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, assessed the frequency of approval and marketing of skinny-label biosimilars from 2015 to 2021 and the resultant savings to Medicare.
The authors estimated annual Part B (clinician-administered) savings from skinny-label biosimilars through 2020 by comparing actual biologic and skinny-label biosimilar spending with estimated biologic spending without competition using the Medicare Dashboard. They assumed that the unit price of the biologic would increase at its 5-year compound annual growth rate prior to competition.
In that period, the FDA approved 33 biosimilars linked to 11 biologics. Among them, 22 (66.7%) had a skinny label. Of 21 biosimilars marketed before 2022, 13 (61.9%) were launched with a skinny label. Of the 8 biologics linked to these 21 biosimilars, 5 of the first-to-market biosimilars had skinny labels (bevacizumab, filgrastim, infliximab, pegfilgrastim, and rituximab), leading to earlier competition through 2021.
The estimated $1.5 billion in savings to Medicare from these skinny-label biosimilars over the 2015-2020 span represents 4.9% of the $30.2 billion that Medicare spent on the five biologics during this period. The researchers pointed out that once adalimumab (Humira) faces skinny-label biosimilar competition in 2023, savings will likely grow substantially.
In response to the research letter, an editor’s note by JAMA Internal Medicine Editorial Fellow Eric Ward, MD, and JAMA Internal Medicine Editor at Large and Online Editor Robert Steinbrook, MD, stated that, between 2015 and 2019, 24 (43%) of 56 brand-name drugs had competition from skinny-labeled generic formulations after first becoming available as generics.
The editors also referenced a JAMA Viewpoints article from 2021 that reviewed the most recent case challenging the skinny-label pathway in which GlaxoSmithKline sued Teva for its marketing of a skinny-label generic of the brand-name beta-blocker carvedilol (Coreg) that the plaintive claimed “induced physicians to prescribe carvedilol for indications that had been carved out by Teva’s skinny label, thus infringing GlaxoSmithKline’s patents.” A $235 million judgment against Teva was overturned by a district court and then reversed again by a Federal Circuit court that, after receiving criticism, reconsidered the case, and a panel affirmed the judgment against Teva.
“The Federal Circuit panel’s decision has the potential to put generic drugs that fail to adequately carve out indications from the brand name labeling at risk for damages related to infringement,” the authors wrote. Similar claims of infringement are being heard in other courts, they wrote, and they urged careful targeting of skinny-label carveouts, and suggest also that challenges to the arguments used against Teva focus on preservation of First Amendment rights as protection for lawful and accurate speech in drug labels.
“The legal uncertainties are likely to continue, as manufacturers pursue novel and complex strategies to protect the patents and regulatory exclusivities of brand-name drugs and biologics,” Dr. Ward and Dr. Steinbrook wrote, adding that “the path forward is for Congress to enact additional legislation that reaffirms and strengthens the permissibility of skinny labeling.”
The research letter’s corresponding author, Ameet Sarpatwari, PhD, JD, assistant professor at Harvard Medical School, and assistant director for the Harvard Program On Regulation, Therapeutics, And Law, echoed concerns over the Teva case in an interview. “There has certainly been concern that should the appellate decision stand, there will be a chilling effect. As the lone dissenter in that case noted, ‘no skinny-label generic is safe.’ I think many generic and biosimilar manufacturers are awaiting to see whether the Supreme Court will take the case.”
He added: “I do not believe the likelihood of skinny-label-supportive legislation making it through Congress will be greatly diminished in a divided Congress. Democrats and Republicans alike should seek to promote competition in the marketplace, which is what the skinny-labeling pathway accomplishes.”
The authors reported no relevant conflicts of interest. The research was funded by a grant from Arnold Ventures.
Competition between five biologic drugs and their skinny-label biosimilars saved Medicare an estimated $1.5 billion during 2015-2020. But these savings accruing to Medicare and the availability of those and other biosimilars through skinny labeling is under threat from recent court rulings, according to a research letter published online in JAMA Internal Medicine.
The authors highlighted the need for such savings by noting that, while biologics comprise less than 5% of prescription drug use, their price tag amounts to about 40% of U.S. drug spending, Biologic manufacturers often delay the availability of biosimilars for additional years beyond the original patent expiration through further patents for supplemental indications. To provide a counterbalance, federal law allows the Food and Drug Administration to approve “skinny-label” generics and biosimilars that carve out patent-protected indications or regulatory exclusivities. But once a generic drug reaches the market through this process with a skinny label, it may often be substituted for indications that go beyond the ones listed on the skinny label. In fact, some state laws mandate that pharmacists substitute interchangeable generics for brand-name drugs, helping to decrease drug prices. In response to legal threats to the skinny-label pathway, Alexander C. Egilman and colleagues at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, assessed the frequency of approval and marketing of skinny-label biosimilars from 2015 to 2021 and the resultant savings to Medicare.
The authors estimated annual Part B (clinician-administered) savings from skinny-label biosimilars through 2020 by comparing actual biologic and skinny-label biosimilar spending with estimated biologic spending without competition using the Medicare Dashboard. They assumed that the unit price of the biologic would increase at its 5-year compound annual growth rate prior to competition.
In that period, the FDA approved 33 biosimilars linked to 11 biologics. Among them, 22 (66.7%) had a skinny label. Of 21 biosimilars marketed before 2022, 13 (61.9%) were launched with a skinny label. Of the 8 biologics linked to these 21 biosimilars, 5 of the first-to-market biosimilars had skinny labels (bevacizumab, filgrastim, infliximab, pegfilgrastim, and rituximab), leading to earlier competition through 2021.
The estimated $1.5 billion in savings to Medicare from these skinny-label biosimilars over the 2015-2020 span represents 4.9% of the $30.2 billion that Medicare spent on the five biologics during this period. The researchers pointed out that once adalimumab (Humira) faces skinny-label biosimilar competition in 2023, savings will likely grow substantially.
In response to the research letter, an editor’s note by JAMA Internal Medicine Editorial Fellow Eric Ward, MD, and JAMA Internal Medicine Editor at Large and Online Editor Robert Steinbrook, MD, stated that, between 2015 and 2019, 24 (43%) of 56 brand-name drugs had competition from skinny-labeled generic formulations after first becoming available as generics.
The editors also referenced a JAMA Viewpoints article from 2021 that reviewed the most recent case challenging the skinny-label pathway in which GlaxoSmithKline sued Teva for its marketing of a skinny-label generic of the brand-name beta-blocker carvedilol (Coreg) that the plaintive claimed “induced physicians to prescribe carvedilol for indications that had been carved out by Teva’s skinny label, thus infringing GlaxoSmithKline’s patents.” A $235 million judgment against Teva was overturned by a district court and then reversed again by a Federal Circuit court that, after receiving criticism, reconsidered the case, and a panel affirmed the judgment against Teva.
“The Federal Circuit panel’s decision has the potential to put generic drugs that fail to adequately carve out indications from the brand name labeling at risk for damages related to infringement,” the authors wrote. Similar claims of infringement are being heard in other courts, they wrote, and they urged careful targeting of skinny-label carveouts, and suggest also that challenges to the arguments used against Teva focus on preservation of First Amendment rights as protection for lawful and accurate speech in drug labels.
“The legal uncertainties are likely to continue, as manufacturers pursue novel and complex strategies to protect the patents and regulatory exclusivities of brand-name drugs and biologics,” Dr. Ward and Dr. Steinbrook wrote, adding that “the path forward is for Congress to enact additional legislation that reaffirms and strengthens the permissibility of skinny labeling.”
The research letter’s corresponding author, Ameet Sarpatwari, PhD, JD, assistant professor at Harvard Medical School, and assistant director for the Harvard Program On Regulation, Therapeutics, And Law, echoed concerns over the Teva case in an interview. “There has certainly been concern that should the appellate decision stand, there will be a chilling effect. As the lone dissenter in that case noted, ‘no skinny-label generic is safe.’ I think many generic and biosimilar manufacturers are awaiting to see whether the Supreme Court will take the case.”
He added: “I do not believe the likelihood of skinny-label-supportive legislation making it through Congress will be greatly diminished in a divided Congress. Democrats and Republicans alike should seek to promote competition in the marketplace, which is what the skinny-labeling pathway accomplishes.”
The authors reported no relevant conflicts of interest. The research was funded by a grant from Arnold Ventures.
FROM JAMA INTERNAL MEDICINE
AGA Clinical Practice Update: Surveillance and screening in Barrett’s esophagus
(BE). It also suggests that patients with no symptoms of chronic reflux can be considered for screening, which could significantly increase the number of people eligible for screening.
Current AGA guidelines support endoscopic screening for BE followed by surveillance for the early detection of BE, dysplasia, and neoplasia. However, fewer than 20% of patients eventually diagnosed with esophageal adenocarcinoma (EAC) were previously diagnosed with BE, suggesting that many opportunities for early detection are missed.
The clinical practice update, published online in Clinical Gastroenterology and Hepatology, represents an effort to highlight advances in screening and surveillance with the goal of improving uptake. The main thrust of the document is risk factors other than gastroesophageal reflux disease (GERD) when considering candidates for screening.
In practice, physicians are already starting to employ other risk factors to select patients for screening, according to coauthor Srinadh Komanduri, MD, who is a professor of medicine and surgery at Northwestern University, Chicago. Specifically, the update suggests screening for individuals with at least three established risk factors for EAC and BE. Risk factors include male sex, non-Hispanic White race, age over 50 years, history of smoking, chronic GERD, obesity, or a family history of BE or EAC.
Another purpose of the update is to highlight noninvasive screening tools, especially nonendoscopic cell collection devices. The authors stress that upper endoscopy with biopsies remains the preferred method for BE diagnosis, but methods that are simple, patient-friendly, and cost-effective have the potential to increase the screened population. One option is transnasal endoscopy, which can be performed in the office with no sedation, but this is expensive and requires expertise.
Recently developed nonendoscopic cell collection devices include Cytosponge (Medtronic GI Solutions), EsoCheck (Lucid Diagnostics), and EsophaCap (Capnostics). All are safe and well-tolerated, and they have good sensitivity for BE. The Cytosponge consists of a swallowable piece of polyurethane foam fitted into a capsule that is attached to suture. The capsule dissolves and the foam expands, collecting cells, and is then withdrawn. It has undergone extensive testing in BE screening in the United Kingdom and was found to have a sensitivity of 80% and specificity of 92.2%. A primary care study showed a 10-fold increase in BE detection compared with usual care.
The EsophaCap works similarly to the Cytosponge but with a smaller diameter. It has 93% sensitivity and 93% specificity for intestinal metaplasia when combined with a panel of five methylated DNA biomarkers.
The EsoCheck device consists of a balloon attached to a catheter, which is inflated and withdrawn. Ridges on the balloon surface capture cells for analysis. A pilot study using two biomarkers found a 90.3% sensitivity and 91.7% specificity.
The update also advises use of high-definition white light endoscopy (HD-WLE) and virtual chromoendoscopy (VC) for screening and surveillance. An updated meta-analysis showed the two methods combined led to a higher detection rate of high grade dysplasia/EAC than HD-WLE alone (14.7% versus 10.1%; relative risk, 1.44). VC and traditional chromoendoscopy have similar dysplasia detection rates, but the former is recommended since it is readily available, requires no extra costs, and avoids issues that can affect dye-based chromoendoscopy. VC from any manufacturer is acceptable, but most data supporting its utility focuses on narrow-band imaging only.
The authors of the update did not suggest a minimum procedure time because of insufficient data, but they noted that the European Society for Gastrointestinal Endoscopy and United European Gastroenterology recommend a minimum of 7 minutes for upper endoscopy and a minimum of 1 minute per centimeter of the circumferential extent of the Barrett’s mucosa.
The update advises use of the Seattle biopsy protocol for sample during screening and surveillance exams. This includes four-quadrant biopsies taken every 1-2 cm, as well as biopsies from visible lesions. This protocol, however, is not followed in up to 20% of procedures, according to one study. Conceding that fact, the authors also suggest the use of wide area transepithelial sampling (WATS-3D) as a supplementary technique for BE segment sampling.
The Seattle biopsy protocol is associated with a higher dysplasia detection rate (RR, 2.75). This criterion can still be met even if an endoscopist chooses to send a patient for endoscopic resection rather than sample a visible lesion.
(BE). It also suggests that patients with no symptoms of chronic reflux can be considered for screening, which could significantly increase the number of people eligible for screening.
Current AGA guidelines support endoscopic screening for BE followed by surveillance for the early detection of BE, dysplasia, and neoplasia. However, fewer than 20% of patients eventually diagnosed with esophageal adenocarcinoma (EAC) were previously diagnosed with BE, suggesting that many opportunities for early detection are missed.
The clinical practice update, published online in Clinical Gastroenterology and Hepatology, represents an effort to highlight advances in screening and surveillance with the goal of improving uptake. The main thrust of the document is risk factors other than gastroesophageal reflux disease (GERD) when considering candidates for screening.
In practice, physicians are already starting to employ other risk factors to select patients for screening, according to coauthor Srinadh Komanduri, MD, who is a professor of medicine and surgery at Northwestern University, Chicago. Specifically, the update suggests screening for individuals with at least three established risk factors for EAC and BE. Risk factors include male sex, non-Hispanic White race, age over 50 years, history of smoking, chronic GERD, obesity, or a family history of BE or EAC.
Another purpose of the update is to highlight noninvasive screening tools, especially nonendoscopic cell collection devices. The authors stress that upper endoscopy with biopsies remains the preferred method for BE diagnosis, but methods that are simple, patient-friendly, and cost-effective have the potential to increase the screened population. One option is transnasal endoscopy, which can be performed in the office with no sedation, but this is expensive and requires expertise.
Recently developed nonendoscopic cell collection devices include Cytosponge (Medtronic GI Solutions), EsoCheck (Lucid Diagnostics), and EsophaCap (Capnostics). All are safe and well-tolerated, and they have good sensitivity for BE. The Cytosponge consists of a swallowable piece of polyurethane foam fitted into a capsule that is attached to suture. The capsule dissolves and the foam expands, collecting cells, and is then withdrawn. It has undergone extensive testing in BE screening in the United Kingdom and was found to have a sensitivity of 80% and specificity of 92.2%. A primary care study showed a 10-fold increase in BE detection compared with usual care.
The EsophaCap works similarly to the Cytosponge but with a smaller diameter. It has 93% sensitivity and 93% specificity for intestinal metaplasia when combined with a panel of five methylated DNA biomarkers.
The EsoCheck device consists of a balloon attached to a catheter, which is inflated and withdrawn. Ridges on the balloon surface capture cells for analysis. A pilot study using two biomarkers found a 90.3% sensitivity and 91.7% specificity.
The update also advises use of high-definition white light endoscopy (HD-WLE) and virtual chromoendoscopy (VC) for screening and surveillance. An updated meta-analysis showed the two methods combined led to a higher detection rate of high grade dysplasia/EAC than HD-WLE alone (14.7% versus 10.1%; relative risk, 1.44). VC and traditional chromoendoscopy have similar dysplasia detection rates, but the former is recommended since it is readily available, requires no extra costs, and avoids issues that can affect dye-based chromoendoscopy. VC from any manufacturer is acceptable, but most data supporting its utility focuses on narrow-band imaging only.
The authors of the update did not suggest a minimum procedure time because of insufficient data, but they noted that the European Society for Gastrointestinal Endoscopy and United European Gastroenterology recommend a minimum of 7 minutes for upper endoscopy and a minimum of 1 minute per centimeter of the circumferential extent of the Barrett’s mucosa.
The update advises use of the Seattle biopsy protocol for sample during screening and surveillance exams. This includes four-quadrant biopsies taken every 1-2 cm, as well as biopsies from visible lesions. This protocol, however, is not followed in up to 20% of procedures, according to one study. Conceding that fact, the authors also suggest the use of wide area transepithelial sampling (WATS-3D) as a supplementary technique for BE segment sampling.
The Seattle biopsy protocol is associated with a higher dysplasia detection rate (RR, 2.75). This criterion can still be met even if an endoscopist chooses to send a patient for endoscopic resection rather than sample a visible lesion.
(BE). It also suggests that patients with no symptoms of chronic reflux can be considered for screening, which could significantly increase the number of people eligible for screening.
Current AGA guidelines support endoscopic screening for BE followed by surveillance for the early detection of BE, dysplasia, and neoplasia. However, fewer than 20% of patients eventually diagnosed with esophageal adenocarcinoma (EAC) were previously diagnosed with BE, suggesting that many opportunities for early detection are missed.
The clinical practice update, published online in Clinical Gastroenterology and Hepatology, represents an effort to highlight advances in screening and surveillance with the goal of improving uptake. The main thrust of the document is risk factors other than gastroesophageal reflux disease (GERD) when considering candidates for screening.
In practice, physicians are already starting to employ other risk factors to select patients for screening, according to coauthor Srinadh Komanduri, MD, who is a professor of medicine and surgery at Northwestern University, Chicago. Specifically, the update suggests screening for individuals with at least three established risk factors for EAC and BE. Risk factors include male sex, non-Hispanic White race, age over 50 years, history of smoking, chronic GERD, obesity, or a family history of BE or EAC.
Another purpose of the update is to highlight noninvasive screening tools, especially nonendoscopic cell collection devices. The authors stress that upper endoscopy with biopsies remains the preferred method for BE diagnosis, but methods that are simple, patient-friendly, and cost-effective have the potential to increase the screened population. One option is transnasal endoscopy, which can be performed in the office with no sedation, but this is expensive and requires expertise.
Recently developed nonendoscopic cell collection devices include Cytosponge (Medtronic GI Solutions), EsoCheck (Lucid Diagnostics), and EsophaCap (Capnostics). All are safe and well-tolerated, and they have good sensitivity for BE. The Cytosponge consists of a swallowable piece of polyurethane foam fitted into a capsule that is attached to suture. The capsule dissolves and the foam expands, collecting cells, and is then withdrawn. It has undergone extensive testing in BE screening in the United Kingdom and was found to have a sensitivity of 80% and specificity of 92.2%. A primary care study showed a 10-fold increase in BE detection compared with usual care.
The EsophaCap works similarly to the Cytosponge but with a smaller diameter. It has 93% sensitivity and 93% specificity for intestinal metaplasia when combined with a panel of five methylated DNA biomarkers.
The EsoCheck device consists of a balloon attached to a catheter, which is inflated and withdrawn. Ridges on the balloon surface capture cells for analysis. A pilot study using two biomarkers found a 90.3% sensitivity and 91.7% specificity.
The update also advises use of high-definition white light endoscopy (HD-WLE) and virtual chromoendoscopy (VC) for screening and surveillance. An updated meta-analysis showed the two methods combined led to a higher detection rate of high grade dysplasia/EAC than HD-WLE alone (14.7% versus 10.1%; relative risk, 1.44). VC and traditional chromoendoscopy have similar dysplasia detection rates, but the former is recommended since it is readily available, requires no extra costs, and avoids issues that can affect dye-based chromoendoscopy. VC from any manufacturer is acceptable, but most data supporting its utility focuses on narrow-band imaging only.
The authors of the update did not suggest a minimum procedure time because of insufficient data, but they noted that the European Society for Gastrointestinal Endoscopy and United European Gastroenterology recommend a minimum of 7 minutes for upper endoscopy and a minimum of 1 minute per centimeter of the circumferential extent of the Barrett’s mucosa.
The update advises use of the Seattle biopsy protocol for sample during screening and surveillance exams. This includes four-quadrant biopsies taken every 1-2 cm, as well as biopsies from visible lesions. This protocol, however, is not followed in up to 20% of procedures, according to one study. Conceding that fact, the authors also suggest the use of wide area transepithelial sampling (WATS-3D) as a supplementary technique for BE segment sampling.
The Seattle biopsy protocol is associated with a higher dysplasia detection rate (RR, 2.75). This criterion can still be met even if an endoscopist chooses to send a patient for endoscopic resection rather than sample a visible lesion.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Wide variance described in lab monitoring of conventional synthetic DMARDs
Rheumatologists tend to order the same types of tests to monitor their patients’ responses to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), but they vary widely in how often they order tests and how they respond to abnormal results, responses to a survey suggest.
“The study found that, although guidelines exist, people didn’t follow them consistently. They also responded to abnormal test results in wildly different ways,” senior study author Philip C. Robinson, MBChB, PhD, of the University of Queensland, Herston, Australia, said in an interview.
“The take-home message of this study is that everyone is doing something different, which means that the system likely has a lot of low-value activity and that money is being wasted,” he added. “However, we don’t have the evidence to guide people to make better choices.”
The literature on laboratory monitoring of people taking csDMARDs for rheumatic disease is scant, the authors wrote in BMC Rheumatology, and current guidelines on csDMARD monitoring vary, likely because of the lack of high-quality evidence for specific monitoring regimens.
“An enormous amount of money is spent on DMARD monitoring with little evidence to support current practices,” Dr. Robinson said. So he and his colleagues asked rheumatologists and rheumatology trainees about their attitudes and practices related to laboratory monitoring of csDMARDs in an online questionnaire.
They used the Australian Rheumatology Association newsletter to invite around 530 Australian rheumatologists and trainees, around 4,500 of Dr. Robinson’s Twitter followers, and 25 Australian and overseas email contacts, to respond to questions about csDMARDs they prescribed, frequency and patterns of monitoring, influences of additional factors and combination therapy, responses to abnormal tests, and attitudes toward monitoring frequency.
The researchers based their questions on csDMARD monitoring guidelines published by the American College of Rheumatology (which recommends monitoring every 2-4 weeks from initiation to 3 months, every 8-12 weeks during months 3-6, and every 12 weeks from 6 months onward), and from the British Society for Rheumatology (whose guidance is similar but bases monitoring frequency on how long DMARD doses remain stable).
The 221 valid responses they collected included 53 from Australia and 39 from the United States. Overall, 53% of respondents were in public practice, 56% were women, and 56% had practiced rheumatology for 11 or more years.
Respondents reported more frequent monitoring of patients with multiple comorbidities and those taking csDMARD combinations, including methotrexate and leflunomide. Responses to abnormal monitoring results varied widely, and 40% of respondents reported that monitoring tests are performed too often. Compared with females, males reported greater tolerance of significant test abnormalities before acting. They also were more likely to report that guidelines recommend, and doctors perform, tests too frequently.
Testing, monitoring patterns can differ from current guidelines
Rheumatologists who were asked to comment on the survey welcomed its results.
They came as no surprise to Daniel E. Furst, MD, professor emeritus of medicine at the University of California, Los Angeles.
“Most guidelines point out in the introduction that they are recommendations and need to be modified by specific patient and environmental needs,” he noted in an interview.
Stephen Myers, MD, assistant professor of clinical medicine in the division of rheumatology at the University of Southern California, Los Angeles, said: “The findings seem generally consistent with my observed practices and those of my peers, with the exception of sulfasalazine, which we tend to monitor every 3 months, similar to the way we monitor other csDMARDs.”
Caoilfhionn Connolly, MD, MSc, postdoctoral fellow in rheumatology at Johns Hopkins University, Baltimore, called “the variability in monitoring somewhat surprising given that both the American College of Rheumatology and the British Society for Rheumatology provide guidance statements on optimal monitoring.
“As the authors highlight,” she added, “the variability in monitoring and response to lab abnormalities is likely driven by the lack of a high-quality evidence base, which should ideally be derived from clinical trials.”
Medication monitoring is critical to ensuring patient safety in rheumatology and other specialties, said Puja Khanna, MD, MPH, a rheumatologist and clinical associate professor of medicine at the University of Michigan, Ann Arbor.
Dr. Khanna described how in 2018, the Michigan Medicine health care system revisited its processes and protocols for medication monitoring.
Previously, “we were reliant on society guidelines that were not used consistently across the academic and community rheumatology practices,” she said. “Using lean thinking methodology, we found that we lacked familiarity with laboratory monitoring protocols amongst the interdisciplinary teams involved in the process and that we had a clear need for consensus.
“A consistent departmental protocol was created to help streamline the workflow for ancillary support staff, to close identified operational gaps, and to reduce delays in monitoring that impacted safe practice patterns,” Dr. Khanna added.
“We developed standardized medication- and disease-based monitoring protocols for eight medical specialties, where the person who writes a prescription that requires monitoring can utilize standard work flows to enroll the patient in the medication monitoring program and have dedicated ancillary support staff follow the results periodically and alert clinicians in a timely manner,” she explained. “Almost 15,000 patients are currently monitored in this collaborative program involving clinicians, nurses, pharmacists, and IT and administrative teams.”
Guidelines may not capture clinical realities of csDMARD monitoring
Dr. Myers and colleagues may monitor testing more intensively if, for example, a patient becomes ill, has side effects, or has taken medication incorrectly. But they’ll less intensively monitor a patient who’s been stable on a csDMARD.
“In my current academic practice, deciding lab monitoring frequency is left up to physicians. In my previous private practice experience, lab monitoring seemed to be more frequent than the current guidelines for many patients, compared to public or academic practice,” he said. “It would be interesting to compare monitoring practices in private, public, and academic settings.
“The clinical reality is that frequent monitoring depends on the regular follow-up, which for some patients is difficult, due to socioeconomic factors including lack of childcare and public transport,” Dr. Myers added.
Dr. Khanna mentioned that “guidelines tend to provide details of extant practice patterns, usually taken from evidence-based data. With monitoring, however, that is tough to achieve, unless substantial data can be found in large national registries of patients on immunosuppressive medications.”
Experience and comfort with using immunosuppressive medications, and medicolegal liability considerations, especially because many immunomodulatory agents confer adverse effects, can contribute to clinicians’ behaviors varying from guidelines, she added.
A good scoping review, and further research needed
“This article did what it was supposed to do: Define the various approaches to monitoring,” Dr. Furst said. “It is the next steps that will make a difference in practice.
“Next steps ... may require delving into large observational data sets such as registries to ascertain the consequences of different monitoring strategies for various patient groups and disparate drugs and drug combinations,” added Dr. Furst, who coauthored a 2017 review summarizing guidelines for laboratory monitoring in patients with rheumatoid arthritis.
“A significant oversight is the lack of consideration regarding monitoring for corticosteroids, which are well known to have very consequential adverse events and require careful monitoring,” Dr. Furst observed.
“The difference between men’s and women’s monitoring strategies is of some interest,” he added, “but will only be important if it leads to an understanding of and change in monitoring recommendations.”
Dr. Connolly also noted the differences in strategies between male and female respondents.
“Of interest, male respondents were more likely to feel that monitoring was performed too frequently and were also more tolerant of significant abnormalities,” she said. “This begs the question of whether rheumatologist gender differentially impacts other areas of clinical practice.”
Despite the small sample size that limits generalizability, the results provide preliminary insight into the varied practices among rheumatologists worldwide, Dr. Connolly added.
“Given the frequency of csDMARD prescription, the study highlights the clinical unmet need for a more robust evidence base to guide clinical practice,” she said. “The study also adds to important efforts to provide high-value care to patients with rheumatic diseases and may form the basis for larger studies to facilitate the pragmatic utilization of lab monitoring and ultimately optimize both the quality and value of rheumatological care globally.”
Dr. Robinson and coauthors urged further research. “We need more studies of higher quality to help inform the best strategy for protecting our patients from harm from our commonly used rheumatic medicines,” he said.
Dr. Robinson and two coauthors reported relationships with pharmaceutical companies. The remaining authors and all uninvolved sources, who commented by email, reported no relevant relationships. The study received no funding.
Rheumatologists tend to order the same types of tests to monitor their patients’ responses to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), but they vary widely in how often they order tests and how they respond to abnormal results, responses to a survey suggest.
“The study found that, although guidelines exist, people didn’t follow them consistently. They also responded to abnormal test results in wildly different ways,” senior study author Philip C. Robinson, MBChB, PhD, of the University of Queensland, Herston, Australia, said in an interview.
“The take-home message of this study is that everyone is doing something different, which means that the system likely has a lot of low-value activity and that money is being wasted,” he added. “However, we don’t have the evidence to guide people to make better choices.”
The literature on laboratory monitoring of people taking csDMARDs for rheumatic disease is scant, the authors wrote in BMC Rheumatology, and current guidelines on csDMARD monitoring vary, likely because of the lack of high-quality evidence for specific monitoring regimens.
“An enormous amount of money is spent on DMARD monitoring with little evidence to support current practices,” Dr. Robinson said. So he and his colleagues asked rheumatologists and rheumatology trainees about their attitudes and practices related to laboratory monitoring of csDMARDs in an online questionnaire.
They used the Australian Rheumatology Association newsletter to invite around 530 Australian rheumatologists and trainees, around 4,500 of Dr. Robinson’s Twitter followers, and 25 Australian and overseas email contacts, to respond to questions about csDMARDs they prescribed, frequency and patterns of monitoring, influences of additional factors and combination therapy, responses to abnormal tests, and attitudes toward monitoring frequency.
The researchers based their questions on csDMARD monitoring guidelines published by the American College of Rheumatology (which recommends monitoring every 2-4 weeks from initiation to 3 months, every 8-12 weeks during months 3-6, and every 12 weeks from 6 months onward), and from the British Society for Rheumatology (whose guidance is similar but bases monitoring frequency on how long DMARD doses remain stable).
The 221 valid responses they collected included 53 from Australia and 39 from the United States. Overall, 53% of respondents were in public practice, 56% were women, and 56% had practiced rheumatology for 11 or more years.
Respondents reported more frequent monitoring of patients with multiple comorbidities and those taking csDMARD combinations, including methotrexate and leflunomide. Responses to abnormal monitoring results varied widely, and 40% of respondents reported that monitoring tests are performed too often. Compared with females, males reported greater tolerance of significant test abnormalities before acting. They also were more likely to report that guidelines recommend, and doctors perform, tests too frequently.
Testing, monitoring patterns can differ from current guidelines
Rheumatologists who were asked to comment on the survey welcomed its results.
They came as no surprise to Daniel E. Furst, MD, professor emeritus of medicine at the University of California, Los Angeles.
“Most guidelines point out in the introduction that they are recommendations and need to be modified by specific patient and environmental needs,” he noted in an interview.
Stephen Myers, MD, assistant professor of clinical medicine in the division of rheumatology at the University of Southern California, Los Angeles, said: “The findings seem generally consistent with my observed practices and those of my peers, with the exception of sulfasalazine, which we tend to monitor every 3 months, similar to the way we monitor other csDMARDs.”
Caoilfhionn Connolly, MD, MSc, postdoctoral fellow in rheumatology at Johns Hopkins University, Baltimore, called “the variability in monitoring somewhat surprising given that both the American College of Rheumatology and the British Society for Rheumatology provide guidance statements on optimal monitoring.
“As the authors highlight,” she added, “the variability in monitoring and response to lab abnormalities is likely driven by the lack of a high-quality evidence base, which should ideally be derived from clinical trials.”
Medication monitoring is critical to ensuring patient safety in rheumatology and other specialties, said Puja Khanna, MD, MPH, a rheumatologist and clinical associate professor of medicine at the University of Michigan, Ann Arbor.
Dr. Khanna described how in 2018, the Michigan Medicine health care system revisited its processes and protocols for medication monitoring.
Previously, “we were reliant on society guidelines that were not used consistently across the academic and community rheumatology practices,” she said. “Using lean thinking methodology, we found that we lacked familiarity with laboratory monitoring protocols amongst the interdisciplinary teams involved in the process and that we had a clear need for consensus.
“A consistent departmental protocol was created to help streamline the workflow for ancillary support staff, to close identified operational gaps, and to reduce delays in monitoring that impacted safe practice patterns,” Dr. Khanna added.
“We developed standardized medication- and disease-based monitoring protocols for eight medical specialties, where the person who writes a prescription that requires monitoring can utilize standard work flows to enroll the patient in the medication monitoring program and have dedicated ancillary support staff follow the results periodically and alert clinicians in a timely manner,” she explained. “Almost 15,000 patients are currently monitored in this collaborative program involving clinicians, nurses, pharmacists, and IT and administrative teams.”
Guidelines may not capture clinical realities of csDMARD monitoring
Dr. Myers and colleagues may monitor testing more intensively if, for example, a patient becomes ill, has side effects, or has taken medication incorrectly. But they’ll less intensively monitor a patient who’s been stable on a csDMARD.
“In my current academic practice, deciding lab monitoring frequency is left up to physicians. In my previous private practice experience, lab monitoring seemed to be more frequent than the current guidelines for many patients, compared to public or academic practice,” he said. “It would be interesting to compare monitoring practices in private, public, and academic settings.
“The clinical reality is that frequent monitoring depends on the regular follow-up, which for some patients is difficult, due to socioeconomic factors including lack of childcare and public transport,” Dr. Myers added.
Dr. Khanna mentioned that “guidelines tend to provide details of extant practice patterns, usually taken from evidence-based data. With monitoring, however, that is tough to achieve, unless substantial data can be found in large national registries of patients on immunosuppressive medications.”
Experience and comfort with using immunosuppressive medications, and medicolegal liability considerations, especially because many immunomodulatory agents confer adverse effects, can contribute to clinicians’ behaviors varying from guidelines, she added.
A good scoping review, and further research needed
“This article did what it was supposed to do: Define the various approaches to monitoring,” Dr. Furst said. “It is the next steps that will make a difference in practice.
“Next steps ... may require delving into large observational data sets such as registries to ascertain the consequences of different monitoring strategies for various patient groups and disparate drugs and drug combinations,” added Dr. Furst, who coauthored a 2017 review summarizing guidelines for laboratory monitoring in patients with rheumatoid arthritis.
“A significant oversight is the lack of consideration regarding monitoring for corticosteroids, which are well known to have very consequential adverse events and require careful monitoring,” Dr. Furst observed.
“The difference between men’s and women’s monitoring strategies is of some interest,” he added, “but will only be important if it leads to an understanding of and change in monitoring recommendations.”
Dr. Connolly also noted the differences in strategies between male and female respondents.
“Of interest, male respondents were more likely to feel that monitoring was performed too frequently and were also more tolerant of significant abnormalities,” she said. “This begs the question of whether rheumatologist gender differentially impacts other areas of clinical practice.”
Despite the small sample size that limits generalizability, the results provide preliminary insight into the varied practices among rheumatologists worldwide, Dr. Connolly added.
“Given the frequency of csDMARD prescription, the study highlights the clinical unmet need for a more robust evidence base to guide clinical practice,” she said. “The study also adds to important efforts to provide high-value care to patients with rheumatic diseases and may form the basis for larger studies to facilitate the pragmatic utilization of lab monitoring and ultimately optimize both the quality and value of rheumatological care globally.”
Dr. Robinson and coauthors urged further research. “We need more studies of higher quality to help inform the best strategy for protecting our patients from harm from our commonly used rheumatic medicines,” he said.
Dr. Robinson and two coauthors reported relationships with pharmaceutical companies. The remaining authors and all uninvolved sources, who commented by email, reported no relevant relationships. The study received no funding.
Rheumatologists tend to order the same types of tests to monitor their patients’ responses to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), but they vary widely in how often they order tests and how they respond to abnormal results, responses to a survey suggest.
“The study found that, although guidelines exist, people didn’t follow them consistently. They also responded to abnormal test results in wildly different ways,” senior study author Philip C. Robinson, MBChB, PhD, of the University of Queensland, Herston, Australia, said in an interview.
“The take-home message of this study is that everyone is doing something different, which means that the system likely has a lot of low-value activity and that money is being wasted,” he added. “However, we don’t have the evidence to guide people to make better choices.”
The literature on laboratory monitoring of people taking csDMARDs for rheumatic disease is scant, the authors wrote in BMC Rheumatology, and current guidelines on csDMARD monitoring vary, likely because of the lack of high-quality evidence for specific monitoring regimens.
“An enormous amount of money is spent on DMARD monitoring with little evidence to support current practices,” Dr. Robinson said. So he and his colleagues asked rheumatologists and rheumatology trainees about their attitudes and practices related to laboratory monitoring of csDMARDs in an online questionnaire.
They used the Australian Rheumatology Association newsletter to invite around 530 Australian rheumatologists and trainees, around 4,500 of Dr. Robinson’s Twitter followers, and 25 Australian and overseas email contacts, to respond to questions about csDMARDs they prescribed, frequency and patterns of monitoring, influences of additional factors and combination therapy, responses to abnormal tests, and attitudes toward monitoring frequency.
The researchers based their questions on csDMARD monitoring guidelines published by the American College of Rheumatology (which recommends monitoring every 2-4 weeks from initiation to 3 months, every 8-12 weeks during months 3-6, and every 12 weeks from 6 months onward), and from the British Society for Rheumatology (whose guidance is similar but bases monitoring frequency on how long DMARD doses remain stable).
The 221 valid responses they collected included 53 from Australia and 39 from the United States. Overall, 53% of respondents were in public practice, 56% were women, and 56% had practiced rheumatology for 11 or more years.
Respondents reported more frequent monitoring of patients with multiple comorbidities and those taking csDMARD combinations, including methotrexate and leflunomide. Responses to abnormal monitoring results varied widely, and 40% of respondents reported that monitoring tests are performed too often. Compared with females, males reported greater tolerance of significant test abnormalities before acting. They also were more likely to report that guidelines recommend, and doctors perform, tests too frequently.
Testing, monitoring patterns can differ from current guidelines
Rheumatologists who were asked to comment on the survey welcomed its results.
They came as no surprise to Daniel E. Furst, MD, professor emeritus of medicine at the University of California, Los Angeles.
“Most guidelines point out in the introduction that they are recommendations and need to be modified by specific patient and environmental needs,” he noted in an interview.
Stephen Myers, MD, assistant professor of clinical medicine in the division of rheumatology at the University of Southern California, Los Angeles, said: “The findings seem generally consistent with my observed practices and those of my peers, with the exception of sulfasalazine, which we tend to monitor every 3 months, similar to the way we monitor other csDMARDs.”
Caoilfhionn Connolly, MD, MSc, postdoctoral fellow in rheumatology at Johns Hopkins University, Baltimore, called “the variability in monitoring somewhat surprising given that both the American College of Rheumatology and the British Society for Rheumatology provide guidance statements on optimal monitoring.
“As the authors highlight,” she added, “the variability in monitoring and response to lab abnormalities is likely driven by the lack of a high-quality evidence base, which should ideally be derived from clinical trials.”
Medication monitoring is critical to ensuring patient safety in rheumatology and other specialties, said Puja Khanna, MD, MPH, a rheumatologist and clinical associate professor of medicine at the University of Michigan, Ann Arbor.
Dr. Khanna described how in 2018, the Michigan Medicine health care system revisited its processes and protocols for medication monitoring.
Previously, “we were reliant on society guidelines that were not used consistently across the academic and community rheumatology practices,” she said. “Using lean thinking methodology, we found that we lacked familiarity with laboratory monitoring protocols amongst the interdisciplinary teams involved in the process and that we had a clear need for consensus.
“A consistent departmental protocol was created to help streamline the workflow for ancillary support staff, to close identified operational gaps, and to reduce delays in monitoring that impacted safe practice patterns,” Dr. Khanna added.
“We developed standardized medication- and disease-based monitoring protocols for eight medical specialties, where the person who writes a prescription that requires monitoring can utilize standard work flows to enroll the patient in the medication monitoring program and have dedicated ancillary support staff follow the results periodically and alert clinicians in a timely manner,” she explained. “Almost 15,000 patients are currently monitored in this collaborative program involving clinicians, nurses, pharmacists, and IT and administrative teams.”
Guidelines may not capture clinical realities of csDMARD monitoring
Dr. Myers and colleagues may monitor testing more intensively if, for example, a patient becomes ill, has side effects, or has taken medication incorrectly. But they’ll less intensively monitor a patient who’s been stable on a csDMARD.
“In my current academic practice, deciding lab monitoring frequency is left up to physicians. In my previous private practice experience, lab monitoring seemed to be more frequent than the current guidelines for many patients, compared to public or academic practice,” he said. “It would be interesting to compare monitoring practices in private, public, and academic settings.
“The clinical reality is that frequent monitoring depends on the regular follow-up, which for some patients is difficult, due to socioeconomic factors including lack of childcare and public transport,” Dr. Myers added.
Dr. Khanna mentioned that “guidelines tend to provide details of extant practice patterns, usually taken from evidence-based data. With monitoring, however, that is tough to achieve, unless substantial data can be found in large national registries of patients on immunosuppressive medications.”
Experience and comfort with using immunosuppressive medications, and medicolegal liability considerations, especially because many immunomodulatory agents confer adverse effects, can contribute to clinicians’ behaviors varying from guidelines, she added.
A good scoping review, and further research needed
“This article did what it was supposed to do: Define the various approaches to monitoring,” Dr. Furst said. “It is the next steps that will make a difference in practice.
“Next steps ... may require delving into large observational data sets such as registries to ascertain the consequences of different monitoring strategies for various patient groups and disparate drugs and drug combinations,” added Dr. Furst, who coauthored a 2017 review summarizing guidelines for laboratory monitoring in patients with rheumatoid arthritis.
“A significant oversight is the lack of consideration regarding monitoring for corticosteroids, which are well known to have very consequential adverse events and require careful monitoring,” Dr. Furst observed.
“The difference between men’s and women’s monitoring strategies is of some interest,” he added, “but will only be important if it leads to an understanding of and change in monitoring recommendations.”
Dr. Connolly also noted the differences in strategies between male and female respondents.
“Of interest, male respondents were more likely to feel that monitoring was performed too frequently and were also more tolerant of significant abnormalities,” she said. “This begs the question of whether rheumatologist gender differentially impacts other areas of clinical practice.”
Despite the small sample size that limits generalizability, the results provide preliminary insight into the varied practices among rheumatologists worldwide, Dr. Connolly added.
“Given the frequency of csDMARD prescription, the study highlights the clinical unmet need for a more robust evidence base to guide clinical practice,” she said. “The study also adds to important efforts to provide high-value care to patients with rheumatic diseases and may form the basis for larger studies to facilitate the pragmatic utilization of lab monitoring and ultimately optimize both the quality and value of rheumatological care globally.”
Dr. Robinson and coauthors urged further research. “We need more studies of higher quality to help inform the best strategy for protecting our patients from harm from our commonly used rheumatic medicines,” he said.
Dr. Robinson and two coauthors reported relationships with pharmaceutical companies. The remaining authors and all uninvolved sources, who commented by email, reported no relevant relationships. The study received no funding.
FROM BMC RHEUMATOLOGY
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Commentary: Evaluating colonoscopy in CRC, December 2022
As usual, several provocative additions to the colorectal cancer literature were published last month, but I will review only one today: the NordICC trial. This trial evaluated the use of screening colonoscopy to reduce the incidence of colorectal cancer, death from colorectal cancer, and all-cause mortality.
We have long accepted that colonoscopy is the gold standard for detection of colorectal cancer, but until the publication of this study there has never been a prospective, randomized controlled clinical trial to evaluate the efficacy of the test. Nearly 85,000 men and women from Nordic nations were randomly assigned to receive an invitation for either screening colonoscopy or usual care (ie, no colonoscopy). In the intention-to-screen analysis, colonoscopy reduced the risk for colorectal cancer over a period of 10 years by 18% (relative risk [RR] 0.82; 95% CI 0.70-0.93). However, the reduction in risk for death from colorectal cancer failed to reach statistical significance (RR 0.90; 95% CI 0.64-1.16).
These results were especially disappointing because sigmoidoscopy, a test that evaluates only the rectum and left colon, has been shown in multiple studies to reduce risk for colorectal cancer death and all-cause mortality. It is difficult for me to think of a biologically plausible explanation for colonoscopy to be less effective than sigmoidoscopy in the prevention of cause-specific and all-cause death. However, potential explanations are hidden in the study data. Most glaringly, only 42% of the colonoscopy invitees received a colonoscopy as compared with a much larger percentage of patients (58%-87%) in the sigmoidoscopy trials. While this might be an important real-world data point, it is far less than the estimated 60% of patients in the United States who adhere to the recommendation for screening colonoscopy from ages 45 to 55. Additionally, the study had only 10 years of follow-up. It is possible that this is just not long enough for the benefits of screening colonoscopy to be fully realized. Finally, 29% of endoscopists had an adenoma detection below the recommended threshold of 25%, suggesting that poor colonoscopic technique may have played a role in the limited efficacy of colonoscopy found in the study.
Regardless of what we think of these results, the study was generally well designed and, therefore, very important. Studies like this give us critical information that we, as a nation, need to determine how best to allot our limited healthcare resources. While this study does not change my perception of the efficacy of colonoscopy, it makes me think twice about its societal utility.
As usual, several provocative additions to the colorectal cancer literature were published last month, but I will review only one today: the NordICC trial. This trial evaluated the use of screening colonoscopy to reduce the incidence of colorectal cancer, death from colorectal cancer, and all-cause mortality.
We have long accepted that colonoscopy is the gold standard for detection of colorectal cancer, but until the publication of this study there has never been a prospective, randomized controlled clinical trial to evaluate the efficacy of the test. Nearly 85,000 men and women from Nordic nations were randomly assigned to receive an invitation for either screening colonoscopy or usual care (ie, no colonoscopy). In the intention-to-screen analysis, colonoscopy reduced the risk for colorectal cancer over a period of 10 years by 18% (relative risk [RR] 0.82; 95% CI 0.70-0.93). However, the reduction in risk for death from colorectal cancer failed to reach statistical significance (RR 0.90; 95% CI 0.64-1.16).
These results were especially disappointing because sigmoidoscopy, a test that evaluates only the rectum and left colon, has been shown in multiple studies to reduce risk for colorectal cancer death and all-cause mortality. It is difficult for me to think of a biologically plausible explanation for colonoscopy to be less effective than sigmoidoscopy in the prevention of cause-specific and all-cause death. However, potential explanations are hidden in the study data. Most glaringly, only 42% of the colonoscopy invitees received a colonoscopy as compared with a much larger percentage of patients (58%-87%) in the sigmoidoscopy trials. While this might be an important real-world data point, it is far less than the estimated 60% of patients in the United States who adhere to the recommendation for screening colonoscopy from ages 45 to 55. Additionally, the study had only 10 years of follow-up. It is possible that this is just not long enough for the benefits of screening colonoscopy to be fully realized. Finally, 29% of endoscopists had an adenoma detection below the recommended threshold of 25%, suggesting that poor colonoscopic technique may have played a role in the limited efficacy of colonoscopy found in the study.
Regardless of what we think of these results, the study was generally well designed and, therefore, very important. Studies like this give us critical information that we, as a nation, need to determine how best to allot our limited healthcare resources. While this study does not change my perception of the efficacy of colonoscopy, it makes me think twice about its societal utility.
As usual, several provocative additions to the colorectal cancer literature were published last month, but I will review only one today: the NordICC trial. This trial evaluated the use of screening colonoscopy to reduce the incidence of colorectal cancer, death from colorectal cancer, and all-cause mortality.
We have long accepted that colonoscopy is the gold standard for detection of colorectal cancer, but until the publication of this study there has never been a prospective, randomized controlled clinical trial to evaluate the efficacy of the test. Nearly 85,000 men and women from Nordic nations were randomly assigned to receive an invitation for either screening colonoscopy or usual care (ie, no colonoscopy). In the intention-to-screen analysis, colonoscopy reduced the risk for colorectal cancer over a period of 10 years by 18% (relative risk [RR] 0.82; 95% CI 0.70-0.93). However, the reduction in risk for death from colorectal cancer failed to reach statistical significance (RR 0.90; 95% CI 0.64-1.16).
These results were especially disappointing because sigmoidoscopy, a test that evaluates only the rectum and left colon, has been shown in multiple studies to reduce risk for colorectal cancer death and all-cause mortality. It is difficult for me to think of a biologically plausible explanation for colonoscopy to be less effective than sigmoidoscopy in the prevention of cause-specific and all-cause death. However, potential explanations are hidden in the study data. Most glaringly, only 42% of the colonoscopy invitees received a colonoscopy as compared with a much larger percentage of patients (58%-87%) in the sigmoidoscopy trials. While this might be an important real-world data point, it is far less than the estimated 60% of patients in the United States who adhere to the recommendation for screening colonoscopy from ages 45 to 55. Additionally, the study had only 10 years of follow-up. It is possible that this is just not long enough for the benefits of screening colonoscopy to be fully realized. Finally, 29% of endoscopists had an adenoma detection below the recommended threshold of 25%, suggesting that poor colonoscopic technique may have played a role in the limited efficacy of colonoscopy found in the study.
Regardless of what we think of these results, the study was generally well designed and, therefore, very important. Studies like this give us critical information that we, as a nation, need to determine how best to allot our limited healthcare resources. While this study does not change my perception of the efficacy of colonoscopy, it makes me think twice about its societal utility.
Clinical Implications of Partial Response to Antidepressants
Only about one third of patients with major depressive disorder achieve full remission with antidepressant therapy. Another third are considered nonresponders, and the remaining one third are partial responders. The latter group of patients are those who have seen some improvement but have not achieved full remission.
Dr Michael Thase at the Perelman School of Medicine, University of Pennsylvania, discusses the symptomatic burden and risk for relapse faced by partial responders, who present a significant treatment challenge.
Dr Thase explores the therapeutic options available when a first-choice treatment option proves incompletely effective. In addition to medication optimization, adjunctive treatment and alternative approaches are considered.
--
Michael E. Thase, MD, Professor, Department of Psychiatry, Mood and Anxiety Disorders Treatment and Research Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Michael E. Thase, MD, has disclosed the following relevant financial relationships:
Serve(d) as an advisor or consultant for: Acadia, Inc; Akili, Inc;
Alkermes PLC; Allergan, Inc; Axsome Therapeutics, Inc; BioHaven, Inc; Bocemtium Consulting, SL; Boehringer Ingelheim International; CatalYm GmbH; Clexio Biosciences; Gerson Lehrman Group, Inc; H Lundbeck, A/S; Jazz Pharmaceuticals; Janssen; Johnson & Johnson; Luye Pharma Group, Ltd; Merck & Company, Inc; Otsuka Pharmaceuticals Company, Ltd; Pfizer, Inc; Sage Pharmaceuicals; Seelos Pharmaceuticals; Sunovion Pharmaceuticals, Inc; Takeda Pharmaceutical Company, Ltd
Receive research funding from: Acadia, Inc; Allergan, Inc; AssureRx; Axsome Therapeutics, Inc; BioHaven, Inc; Intracellular, Inc; Johnson & Johnson; Otsuka Pharmaceuticals Company, Ltd; Patient-Centered Outcomes Research Institute (PCORI); Takeda Pharmaceutical Company, Ltd
Receive royalties from: American Psychiatric Foundation; Guilford Publications; Herald House; Kluwer-Wolters; W W Norton & Company, Inc
Only about one third of patients with major depressive disorder achieve full remission with antidepressant therapy. Another third are considered nonresponders, and the remaining one third are partial responders. The latter group of patients are those who have seen some improvement but have not achieved full remission.
Dr Michael Thase at the Perelman School of Medicine, University of Pennsylvania, discusses the symptomatic burden and risk for relapse faced by partial responders, who present a significant treatment challenge.
Dr Thase explores the therapeutic options available when a first-choice treatment option proves incompletely effective. In addition to medication optimization, adjunctive treatment and alternative approaches are considered.
--
Michael E. Thase, MD, Professor, Department of Psychiatry, Mood and Anxiety Disorders Treatment and Research Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Michael E. Thase, MD, has disclosed the following relevant financial relationships:
Serve(d) as an advisor or consultant for: Acadia, Inc; Akili, Inc;
Alkermes PLC; Allergan, Inc; Axsome Therapeutics, Inc; BioHaven, Inc; Bocemtium Consulting, SL; Boehringer Ingelheim International; CatalYm GmbH; Clexio Biosciences; Gerson Lehrman Group, Inc; H Lundbeck, A/S; Jazz Pharmaceuticals; Janssen; Johnson & Johnson; Luye Pharma Group, Ltd; Merck & Company, Inc; Otsuka Pharmaceuticals Company, Ltd; Pfizer, Inc; Sage Pharmaceuicals; Seelos Pharmaceuticals; Sunovion Pharmaceuticals, Inc; Takeda Pharmaceutical Company, Ltd
Receive research funding from: Acadia, Inc; Allergan, Inc; AssureRx; Axsome Therapeutics, Inc; BioHaven, Inc; Intracellular, Inc; Johnson & Johnson; Otsuka Pharmaceuticals Company, Ltd; Patient-Centered Outcomes Research Institute (PCORI); Takeda Pharmaceutical Company, Ltd
Receive royalties from: American Psychiatric Foundation; Guilford Publications; Herald House; Kluwer-Wolters; W W Norton & Company, Inc
Only about one third of patients with major depressive disorder achieve full remission with antidepressant therapy. Another third are considered nonresponders, and the remaining one third are partial responders. The latter group of patients are those who have seen some improvement but have not achieved full remission.
Dr Michael Thase at the Perelman School of Medicine, University of Pennsylvania, discusses the symptomatic burden and risk for relapse faced by partial responders, who present a significant treatment challenge.
Dr Thase explores the therapeutic options available when a first-choice treatment option proves incompletely effective. In addition to medication optimization, adjunctive treatment and alternative approaches are considered.
--
Michael E. Thase, MD, Professor, Department of Psychiatry, Mood and Anxiety Disorders Treatment and Research Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Michael E. Thase, MD, has disclosed the following relevant financial relationships:
Serve(d) as an advisor or consultant for: Acadia, Inc; Akili, Inc;
Alkermes PLC; Allergan, Inc; Axsome Therapeutics, Inc; BioHaven, Inc; Bocemtium Consulting, SL; Boehringer Ingelheim International; CatalYm GmbH; Clexio Biosciences; Gerson Lehrman Group, Inc; H Lundbeck, A/S; Jazz Pharmaceuticals; Janssen; Johnson & Johnson; Luye Pharma Group, Ltd; Merck & Company, Inc; Otsuka Pharmaceuticals Company, Ltd; Pfizer, Inc; Sage Pharmaceuicals; Seelos Pharmaceuticals; Sunovion Pharmaceuticals, Inc; Takeda Pharmaceutical Company, Ltd
Receive research funding from: Acadia, Inc; Allergan, Inc; AssureRx; Axsome Therapeutics, Inc; BioHaven, Inc; Intracellular, Inc; Johnson & Johnson; Otsuka Pharmaceuticals Company, Ltd; Patient-Centered Outcomes Research Institute (PCORI); Takeda Pharmaceutical Company, Ltd
Receive royalties from: American Psychiatric Foundation; Guilford Publications; Herald House; Kluwer-Wolters; W W Norton & Company, Inc
